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Table 1 Alphabetical list of diseases and related traits with their causative rat genes and the human homologs

From: Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes

Rat Human Comments References
Phenotype Causative
gene namea
Localisationc
Phenotype Ortholog
gene nameb
Localisationc
A) Monogenic traits
 Acidosis (pH homeostasis) Kcnj16T
10, 99.33 Mb
Brugada syndrome (arrhythmias) KCNJ16
17q24.3
The SS KO mutant exhibits hyperventilation at rest and decreased arterial pH, showing that Kcnj16 plays a role in pH regulation, particularly in the ventilatory CO2 chemoreflex; the gene also controls blood pressure: see below, Polygenic traits [47]
 Addiction BdnfT
3, 100.77 Mb
The heterozygous SD KO mutant exhibits no cocaine-seeking behavior, unlike WT rats [48]
 Addiction Cdh13T
19, 50.85 Mb
Substance abuse, behavioral disorders CDH13
16q23.3
The SS KO mutant shows a stronger responsiveness to cocaine, metamphetamine and saccharin [49]
 Addiction: opioid consumption Grm2T
2q32,
179.58 Mb
The Wistar KO mutant shows higher heroin self-administration and heroin intake as well as reduced sensitivity to cocaine reward; the results suggest that Grm2 may play an inhibitory role in opioid action; see also below, Polygenic traits, Addiction: alcohol consumption [50, 51]
 Adiposity (fat pads) Slc22a18**
1, 216.67 Mb
Positional identification revealed a splicing mutation in the SHR/NCrj rat (which shows reduced fat pad weight); in 3 T3-L1 cells, Slc22a18 KO leads to reduction in lipid accumulation [52]
 Aganglionosis (spotting lethal: sl) Ednrb**
15q22,
88.00 Mb
Hirschsprung disease EDNRB 13q22 Direct analysis of the gene in sl rats revealed a deletion; the mutation was then shown to segregate with the phenotype in congenics; phenotype modulated by modifier genes, including Gdnf; in the GK strain, the null mutant causes embryonic death; see also below, Polygenic traits, Blood pressure: captopril effects [53,54,55,56,57,58,59]
 ALSP Csf1r ALSP CSF1R See Macrophage development [60]
 Amelogenesis imperfecta Sp6**
10q31,
84.96 Mb
Amelogenesis imperfecta SP6
17q21.32
Direct sequencing of the gene revealed an insertional mutation in a mutant SHRSP strain; the mutation was then shown to segregate with the phenotype; partial complementation in Sp6 transgenic rats; in the human, SP6 is one the genes causing Amelogenesis imperfecta [61]
 Analbuminemia Alb**
14p21,
19.18 Mb
Analbuminemia ALB
4q13.3
Direct cloning of the mutant gene revealed a 7 bp deletion at the splicing donor site in intron H of the analbuminemic rat, which does not produce cytoplasmic albumin mRNA [62]
 Anemia (white spotting rat: Ws/Ws) Kit*
14, 35.07 Mb
Direct sequencing of the Kit cDNA revealed a 12 bp deletion in the Ws/Ws strain, by comparison with the BN and SD sequences; the gene also controls coat color and unilateral renal agenesis: see below [63]
 Anemia (Belgrade rat) Slc11a2**
7, 142.03 Mb
Positional identification of the gene (from Belgrade rats) which shows a missense mutation, inactivating iron transport [64]
 Angelman syndrome model Ube3aT
1, 116.59 Mb
Angelman syndrome UBE3A
15q11.2
The SD KO mutant shows delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, impaired touchscreen learning and memory, decreased brain volume and altered neuroanatomy [65]
 Ataxia and seizure (groggy rat) Cacna1a**
19, 25.45 Mb
FHM1, EA2, SCA6 CACNA1A
19p13
Positional identification of the gene which shows a missense mutation in the groggy rat, absent in other strains [66]
 Ataxia- telangiectasia AtmENU, T
8q24,
58.02 Mb
Ataxia- telangectiasia ATM
11q22.3
Rats lacking ATM (missense or KO mutation) display paralysis, neuroinflammation and have significant loss of motor neurons and microgliosis in the spinal cord [67, 68]
 Autism spectrum disorders Cntnap2T
4, 74.70 Mb
Epilepsy (CDFE syndrome) and autism spectrum disorders CNTNAP2
7q35-q36.1
The SD KO mutant shows a delayed maturation of auditory processing pathways and striking parallels to disruptions reported in autism spectrum disorders; see also below: Epilepsy [69]
 Autism spectrum disorders Fmr1T
Xq37,
154.68 Mb
Autism spectrum disorders FMR1
Xq27.3
The SD KO mutant exhibits abnormalities in autism-relevant phenotypes including juvenile play, perseverative behaviors, and sensorimotor gating; see also below, Fragile X syndrome model [70]
 Autism spectrum disorders Nlgn3T
X, 71.20 Mb
Autism spectrum disorders NLGN3
Xq13.1
The SD KO mutant exhibits abnormalities in autism-relevant phenotypes including juvenile play, perseverative behaviors, sensorimotor gating and sleep disruptions [70, 71]
 Autism spectrum disorders Shank2T
1, 217.15 Mb
Autism spectrum disorders SHANK2
11q13.3-q13.4
The SD KO mutant exhibits social and repetitive impairments, as well as a profound phenotype of hyperactivity and hypermotivation that can be ameliorated through the administration of dopamine receptor 1 or metabotropic glutamate receptor 1 antagonists [72]
 Brain development (qc) Lmx1a**
13, 85.92 Mb
Positional identification of the gene, probably involved in the development of the ventricular system and dorsal migration of neurons [73]
 Cancer Brca2ENU
12p12,
0.50 Mb
Breast, ovarian and other cancers BRCA2
13q13.1
The SD KO mutant is sterile and develops a variety of tumors; surprisingly, the female KO rat does not show any increased incidence of mammary carcinomas [74]
 Cancer Msh6ENU
6, 11.64 Mb
Lynch syndrome (HNPCC) MSH6
2p16
Diverse tumors appear in the homozygous Wistar KO mutant; the tumors exhibit microsatellite instability [75]
 Cancer Tp53ENU, T
10q24,
56.19 Mb
Li-Fraumeni syndrome TP53
17p13.1
The heterozygous KO mutants (F344, Wistar, DAc8, SD) develop lymphomas or different types of sarcomas (more typical of human tumors than those found in Tp53 mice mutants), depending on the genetic background; Tp53 also controls Spermatogenesis: see below, Polygenic Traits [76,77,78,79]
 Cancer, colon ApcENU
18p12,
27.01 Mb
Familial colon cancer APC
5q21-q22
Two models are available; the Pirc mutant is homozygous lethal while the heterozygous rat develops polyposis and colon cancers, and thus mimics the human APC-dependent neoplasia (unlike the Apc mutant mice); the KAD mutant is homozygous, viable and shows enhanced susceptibility to colon cancer-inducing agents [80,81,82]
Cancer, multiple endocrine neoplasia-like syndrome X Cdkn1b**,
4q43,
168.69 Mb
Multiple endocrine neoplasia type 4 CDKN1B
12p13.1
Positional identification of the gene (encoding p27Kip1), mutated in the MNX (SDwe)rat; subsequently, a causative mutation was found in theCDKN1Bgene of a patient presenting with pituitary and parathyroid tumors; see also below, Obesity and Polygenic traits, Cancer, mammary gland development [83, 84]
 Cancer, renal carcinoma Flcn**
10, 46.15 Mb
Birt-Hogg-Dube syndrome BHD
17p11.2
Positional identification of the gene: frameshift mutation in the Nihon rat gene, causing a dominant phenotype; LOH in tumors [85]
 Cancer, renal carcinoma (Eker rat) Tsc2**
10q12,
13.96 Mb
Renal carcinoma TSC2
16p3.13
Positional identification of the gene; deletion of the 3′ end of the gene; LOH in tumors, which only express the mutant mRNA [86]
 Cardiac inflammation and fibrosis Sh2b3T
12, 40.26 Mb
Increased risk of myocardial infarction SH2B3
12q24
The SS KO mutant shows exacerbated chronic inflammation and fibrosis post myocardial infarction; the gene also controls blood pressure: see below, Polygenic Traits [87]
 Cardiac ischemia Il1rl2T
9, 47.04 Mb
An SD mutant was generated with cardiac-specific Il1rl2 (Il36r) KO; this mutant shows improved cardiac function, reduced inflammatory response and apoptosis after ischemia-reperfusion [88]
 Cardiac ischemia UbdT
20, 1.87 Mb
The SD KO mutant shows cardiac dysfunction and increased cardiomyocyte apoptosis after myocardial infarction, associated with reduced Cav3 expression; the gene also controls type 1 diabetes (see below) [89]
 Cardiomyopathy Dnmt1T
8, 21.92 Mb
An SD mutant was generated with cardiac-specific Dnmt1 KO; this mutant shows protection against pathological injury induced by adryamycin (increased expression of DNMT1 is observed in familial hypertrophic cardiomyopathy patients) [90]
 Cardiomyopathy (hypertrophic) Myh7bT
3, 151.10 Mb
Hypertrophic cardiomyopathy MYH7B
20q11.22
Mutations were found in a small fraction of human patients; the KO rat mutant shows hypertrophic cardiomyopathy and cardiac fibrosis; the CaMK-signaling pathway is overexpressed in the mutant cardiomyocytes [91]
 Cardiomyopathy(atrial) Myl4T
10, 92.63 Mb
Atrial cardiomyopathy MYL4
17q21.32
The KO mutant reproduces the clinical phenotype, showing atrial arrhythmia, left atrial dilation and progressive atrial fibrosis [40]
 Cardiomyopathy Rbm20**
1, 274.39 Mb
Dilated cardiomyopathy RBM20
10q25.2
Positional identification of the gene; deficiency of Rbm20 alters splicing of several transcripts, such as titin and reduces exercise capacity [92]
 Cataract (NUC1 rat) Cryba1
10, 65.16 Mb
Cataract CRYBA1
17q11.2
Positional identification of the gene: insertion in exon 6 of the NUC1 rat; the mutation is recessive and impairs the development of the retinal pigmented epithelium [93, 94]
 Cataract Crygd**
9q32,
71.77 Mb
Positional identification of the gene: mutation in the start codon of the gene in the SS/Jr-Ctr strain [95]
 Cataract Gja3**
15p12,
41.15 Mb
Cataract GJA3
13q12.11
Positional identification of the gene: non-conservative base substitution in the gene in a SHRSP-derived strain [96]
 Cataract Gja8**
2, 199.05 Mb
Cataract GJA8
1q21
Positional identification of the gene; 2 rat strains show dominant cataract due to non-conservative base substitutions (SHR-Dca and UPL); the SHR-Dca homozygote exhibits microphthalmia; this mutation also lowers blood pressure; see also below, Polygenic Traits, Blood pressure [97, 98]
Cataract Lss**
20, 12.84 Mb
Cataract LSS
21q22.3
Positional identification of the gene: abnormal splicing in the Shumiya cataract rat; phenotype modified byFdft1(15, 50.10 Mb); both genes affect cholesterol synthesis; lanosterol treatment reduces cataract severity [99, 100]
 Cataract (kfrs4 mutation) Mip**
7, 2.64 Mb
Cataract MIP
12q13.3
Positional identification of the gene which, in the mutant, shows a 5 bp insertion leading to a frameshift mutation producing a truncated protein [101]
 Chediak-Higashi syndrome model (beige) Lyst*
17, 90.32 Mb
Chediak-Higashi syndrome 1 LYST
1q42
Direct sequencing of the mutant rat beige gene revealed the presence of a large deletion [102]
 Cerebellar vermis defect (cvd)/ Hobble (hob) Unc5c**
2q44,
247.05 Mb
Positional identification of the gene; the rat mutation is homolog to the mouse rostral cerebellar malformation mutation in the gene encoding netrin receptor C [103]
 Coat color: albinism; siamese Tyr***,T
1q32,
151.01 Mb
Ocolocutaneous albinism TYR
11q14.3
Positional identification of the siamese mutant; an albino DA KO mutant was also generated and correction of the albino mutation was done using the CRISP-Cas system [104,105,106,107]
 Coat color: nonagouti Asip***
3, 150.49 Mb
Cloning of the basis of homology with the mouse variant: deletion in exon 2 of the nonagouti variant; correction of the mutation using the CRISP-Cas system [107, 108]
 Coat color: head spot (KFRS4/Kyo rat) Ednrb**
15q22,
88.00 Mb
Waardenburg syndrome type 4 EDNRB
13q22
Positional identification of the gene; no mutation found in the gene but a deletion was identified upstream the gene in a putative enhancer [109]
 Coat color: hooded (h) and the Ws/Ws rat Kit***
14, 35.07 Mb
Positional identification of the gene: two different insertions found in two alleles (h and hT); correction of the hooded mutation using the CRISP-Cas system; the gene is also mutated in the white spotting rat (Ws/Ws) (no melanocytes) and seems to control anemia (see above); it is also involved in Unilateral renal agenesis (see below) [63, 107, 110]
 Cockayne syndrome (CS) model Ercc6T
16, 8.73 Mb
Cockayne syndrome ERCC6
10q11.23
The SD KO mutant displays DNA repair-deficient phenotypes and brain abnormalities, features that resemble those of CS patients [111]
 Congenital stationary night blindness Cacna1f**
X, 15,71 Mb
Congenital stationary night blindness CACNAIF
Xp11.23
Direct sequencing of the cDNA revealed a mutation generating a stop codon in a strain of spontaneous mutant rat; in a backcross the mutation was found to segregate with the phenotype [112]
 Creeping (cre) Reln**
4q11, 9.35 Mb
Lissencephaly RELN
7q22
Positional identification of the gene, mutated in the KZC rat; the rat mutant is homolog to the mouse reeler [113]
 Cystic fibrosis CftrT
4q21,
42.69 Mb
Cystic fibrosis CFTR
7q31.2
Three mutant strains were described: two KO mutants and a mutant carrying the most frequent human mutation (F508del); they recapitulate many aspects of the human disease (defects in airway mucus production and tracheal development, involution of the vas deferens, intestinal obstruction…..); see also below, Polygenic traits, Bone growth [114, 115]
 Cystic leukoencephalopathy model Rnaset2T
1, 53.17 Mb
Cystic leukoencephalopathy RNASET2
6q27
The SD KO mutant shows no brain cystic lesions but exhibits enlarged prefrontal cortex and hippocampal complex as well as memory deficits (less severe neurodegeneration phenotype than the human patients) [116]
 Cystinosis Ctns**
10, 59.75 Mb
Cystinosis CTNS
17p13.2
Positional identification of the gene, partially deleted in the Long-Evans Agouti rat; the mutation also causes renal glucosuria [117]
 Danon disease model Lamp2T
Xq35,
124.72 Mb
Danon disease LAMP2
Xq24
The SD KO rat shows great similarity to human patients: hypercholesterolemia, hyperglycaemia, cardiomyopathy, and other disorders including retinopathy and chronic kidney injury [118]
 D-amino-acid oxidase deficiency Dao**
12, 48.35 Mb
The LEA rat strain lacks DAO activity; sequencing of the gene revealed a 54.1 Kb deletion in the LEA strain, but not in other strains; a congenic strain carrying the mutant allele in the F344 genetic background was generated: this congenic strain shows defects in D-amino-acids metabolism [119]
 Deafness (dfk: deafness Kyoto) Kncq1**
1q41,
223.15 Mb
Long-QT syndrome, deafness KCNQ1
11p15.5
Positional identification of the gene, partially deleted in the dfk rat, which is also hypertensive [120]
 Deafness Myo7a**
1, 163.00 Mb
Usher syndrome 1B MYO7A 11q13.5 Positional identification of an ENU-induced mutation in the Wistar rat strain (tornado phenotype) [121]
 Deafness; Kyoto circling (kci) Pcdh15**
20, 14.95 Mb
Usher syndrome 1F PCDH15 10q21 Positional identification of the gene, which shows a premature stop codon in the kci mutant [122]
 Deafness, retinal dysfunction Myo15a**
10, 46.84 Mb
Deafness, DFNB3 MYO15A
17p11.2
Positional identification of the gene which shows a non-conservative base substitution in the LEW/Ttm-ci2 rat, causing both deafness and blindness [123]
 Demyelination (see also below: Hypomyelination) AspaT
10, 59.84 Mb
Canavan disease ASPA
17p13.2
The F344 KO mutant shows abnormal myelination in the central nervous system (but no tremor); see also below, Tremor [124]
 Demyelination (les) Mbp*
18, 79.33 Mb
Sequencing of the les Mbp gene revealed that it contains a large insertion altering the splicing of the Mbp RNA [125]
 Demyelination (dmy) Mrs2***
17, 42.64 Mb
Positional identification of the gene; complementation by cDNA transgenesis in the dmy/dmy rat, which carries an inactivating novel splice acceptor site [126]
 Demyelination (md) Plp1**
X, 107.50 Mb
The mutation is linked to the X chromosome; sequencing of the mutant Plp1 cDNA revealed a missense mutation, probably inducing a conformational change in the protein (homologous to the jimpy mouse mutant) [127]
 Demyelination (Taiep) Tubb4a**
9, 9.96 Mb
Hypomyelination TUBB4A
19p13.3
Positional identification of the gene which shows a missense mutation in the Taiep rat [128]
 Diabetes insipidus Avp***
3q35,
123.12 Mb
Neurohypophys-eal diabetes insipidus AVP
20p13
Direct cloning of the gene which shows a single base deletion in the Brattleboro rat; complementation by transgenesis in the hypothalamus [129, 130]
 Diabetes insipidus Stim1**
1, 167.37 Mb
Autoimmunity STIM1
11p15.4
The SHR-A3 strain exhibits nephrogenic diabetes insipidus; genome sequencing revealed a deletion affecting the Stim1 gene is in the SHR-A3 strain, but not in other strains; the phenotype segregates with the mutation, which compromises store-operated calcium entry; this pleiotropic genes also controls Behavior (stress response), Renal injury and Stroke (see Polygenic traits below) [131]
 Dilute-opisthotonus (dop) Myo5a**
8, 82.04 Mb
Griscelli syndrome type I MYO5A
15q21.2
Direct sequencing of the cDNA revealed an in frame, 47aa deletion in the dop Myo5a gene, leading to under-expression of the protein (resulting in diluted coat color and ataxia); a second mutant was identified later by whole genome sequencing: it shows several pleiotropic neuropathological and biochemical alterations leading to neurodegeneration [132, 133]
 Duchenne muscular dystrophy DmdT
Xq22,
51.15 Mb
Duchenne muscular dystrophy DMD
Xp21.2-p21.1
Wistar or SD KO rats show several muscle abnormalities (necrosis, fibrosis, reduced strength, reduced motor activity) and dilated cardiomyopathy [134, 135]
 Drug behavioral effects GhsrENU
2, 113.06 Mb
Cocaine-treated FHH mutant rats shows diminished development of cocaine locomotor sensitization relative to WT rats; see also below, Food intake [136]
 Drug metabolism Abcb1aT
4q12,
22.34 Mb
Wistar or SD KO mutants show increased brain penetration of drugs and other alterations in drug pharmacokinetic parameters [137,138,139,140]
 Drug metabolism Abcg2T
4, 88.76 Mb
The SD KO mutant shows increased brain penetration of drugs and other alterations in drug pharmacokinetic parameters; see also below, Hyperbilirubinemia [138, 139]
 Drug metabolism Cyp2c11T
1q53,
257.68 Mb
The SD KO mutant male shows reduced fertility (CYP2C11 is a male-specific cytochrome P450); expression of other P450’s is upregulated; in vivo, no significant differences were found in drug metabolism [141]
 Drug metabolism Cyp2e1T
1q41,
213.51 Mb
The SD KO rat is physiologically normal, shows a compensatory expression of CYP3A1 and impaired metabolism of chlorzoxazone, a CYP2E1 substrate [142]
 Drug metabolism Cyp3a1T
12, 110.539 Mb
+ Cyp3a2T
12, 116,41 Mb
The double SD KO rat is physiologically normal but shows increased testosterone serum concentrations; it also shows a compensatory expression of several cytochrome isoforms and impaired metabolism towards CYP3A1/2 substrates [143]
 Dwarfism (Spontaneous dwarf rat) Gh**
10q32,
94.48 Mb
Dwarfism GH
17q24
Direct cloning of the gene revealed a point mutation causing abnormal splicing in the Spontaneous dwarf rat [144]
 Dwarfism (mri) Prkg2**
14, 12.22 Mb
Growth retardation Candidate: PRKG2
4q13.1-q21.1
Positional identification of the gene; complementation in cultured chondrocyte by cDNA transfection (restoration of differentiation) [145,146,147]
 Dwarfism (rdw rat) Tg**
7, 107.47 Mb
Sequencing of the Tg cDNA from the rdw rat revealed a missense mutation; rescue from dwarfism was obtained by thyroid function compensation in rdw rats [148, 149]
 Dwarfism (lde/lde rat) Wwox**    See below, Epilepsy  
 Dystonia type 25 GnalT
18q12,
62.80 Mb
Dystonia type 25 GNAL
18p11
The SD KO mutant shows early-onset phenotypes associated with impaired dopamine transmission, such as reduction in locomotor activity and an abnormal motor skill learning ability; it may be a valuable tool for finding a suitable treatment for dystonia type 25 [150]
 Ear and eye development (dumbo mutation) Hmx1**
14, 80.54 Mb
Oculo-auricular syndrome HMX1
4p16.1
Positional identification of the gene; large deletion, 80 kb downstream the dumbo rat gene, which is not expressed in the embryo craniofacial mesenchyme [151]
 Eosinophilia (MES rat) Cyba***
19, 55.25 Mb
Positional identification of the gene; the mutant gene is deleted in the 5′ splice site of intron 4, leading to an abnormal mRNA and absence of NADPH oxidase activity; the normal phenotype was restored by transgenesis of the normal gene [152]
 Epilepsy (flathead rat) Cit**
12, 46.33 Mb
Microcephaly CIT
12q23.24
Positional identification of the gene, which shows a single base deletion in the mutant rat (fh/fh), generating a stop codon; cytokinesis is defective in neuronal progenitors; this mutation also leads to microcephaly (see below) [153, 154]
 Epilepsy Cntnap2T
4, 74.70 Mb
Epilepsy (CDFE syndrome) and autism spectrum disorders CNTNAP2
7q35-q36.1
An SD KO mutant exhibits motor seizures, hyperactivity and increased consolidation of wakefulness and rapid eye movement sleep; see also above: Autism spectrum disorders [155]
 Epilepsy (and ataxia) Kcna1ENU
4q42,
159.19 Mb
Episodic ataxia type 1 KCNA1
12p13.32
An F344 ENU-induced mutant showing dominant myokimia, neuromyotonia and epileptic seizures was used for positional identification of the gene; expression studies in Xenopus oocytes [156]
 Epilepsy (ADLTE mutant) Lgi1ENU
1, 256.95 Mb
Epilepsy (ADLTE) LGI1
10q23.33
The F344 mutant shows early-onset spontaneous epileptic seizures and audiogenic seizure susceptibility; astrocytic Kcnj10 expression is down-regulated [157, 158]
 Epilepsy (febrile seizure; Hiss rat) Scn1aENU
3, 52.39 Mb
Febrile seizure, epilepsy SCN1A 2q24.3 The Hiss mutant shows impaired GABA receptor-mediated synaptic transmission [159]
 Epilepsy Sv2aENU
2, 198.32 Mb
Epilepsy, microcephaly SV2A
1q21.2
The F344 mutant shows a high susceptibility to the development of kindling [160]
 Epilepsy (lde/lde rat) Wwox**
19, 46.76 Mb
Positional identification of the gene, mutated (13 bp deletion) in the lde/lde rat which also shows dwarfism and abnormal testis development (these phenotypes are simultaneously inherited as a single trait) [161]
 Fabry disease model GlaT
X, 105.41 Mb
Fabry disease GLA
Xq22.1
The DA KO mutant manifests symptoms similar to those seen in Fabry patients such as altered touch and pain detection; the sensory neuron cell membrane is sensitized to mechanical probing [162]
 Food intake GhsrENU, T
2, 113.06 Mb
The FHH mutant shows reduced intake of palatable, high-calorie food (see also above, Drug behavioral effects); the Wistar KO rat shows reduced body weight and blunted food consumption [163,164,165]
 Fragile X syndrome model Fmr1T
Xq37,
154.68 Mb
Fragile X syndrome FMR1
Xq27.3
Two SD KO strains are available; they show disrupted cortical processing of auditory stimuli, hippocampal cellular and synaptic deficits, memory defects, abnormal visual responses, impaired spatial learning, attention deficits (deletion of the KH1 domain); see also above, Autism spectrum disorders ([166, 167] and references therein, [168])
 Fused pulmonary lobes (fpl) Frem2**
2, 142.75 Mb
Fraser syndrome FREM2 13q13.3 Direct sequencing of the fpl cDNA showed a premature stop codon; similarity with the mouse Frem2 mutant [169]
 Glycogenosis (PHK deficiency; gsd rat) Phkg2**
1, 199.02 Mb
Glycogenosis PHKG2
16p11.2
Direct sequencing of the human and rat cDNA’s revealed mutations in patients and in the gsd rat [170]
 Hairlessness Hr**
15, 52.24 Mb
Alopecia, atrichia HR
8p21.2
ENU-induced mutant (Kyoto rhino rat) selected on the basis of the phenotype and then positional identification of the gene; the mutant shows hair loss as well as proteinuria and glomerulosclerosis [171]
 Hairlessness Krt@**
7q36, ~ 141 Mb
Positional identification of the locus revealing a 80 kb deletion of several keratin genes in the Hirosaki hairless rats [172]
 Hairlessness (rex mutation) Krt71**
7q36,
143.35 Mb
Positional identification of the gene which has a 7 bp deletion at the splicing acceptor site of the rex intron 1; curly hair in heterozygotes; hair loss in homozygous [173]
 Hairlessness Prss8**
1, 199.37 Mb
Positional identification of the gene: mutations found in affected rats (CR hairless and fuzzy) [174, 175]
 Hairlessness and dermatitis Trpv3**
10, 59.83 Mb
Direct sequencing of the rat cDNA, after positional identification of the mouse gene: dominant, missense mutation in the WBN/Kob-Ht rat and the DS-Nh mouse [176]
 Hemochromatosis Tfr2*
12q12,
22.18 Mb
Hemochromatosis TFR2
7q22
Direct sequencing of the gene revealed an Ala679Gly polymorphism; homozygosity for this SNP is associated with the mutant phenotype in a Hsd:HHCL Wistar stock [177]
 Hemophilia A (WAG-F8m1Ycb) F8**,T
18, 367.17 Mb
Hemophilia A, hemophilic arthropathy F8
Xq28
Evaluation of the individual clotting factors revealed a missense mutation in the factor FVIII cDNA of the mutant rat; the hemostatic defect was corrected by administration of human factor VIII; two KO mutants show an hemophilic phenotype and seems to be good models of hemophilic arthropathy or bone transplantation [178,179,180,181]
 Heriditary tyrosinemia type I model FahT
1, 146.71 Mb
Heriditary tyrosinemia type I FAH
15q25.1
The SD KO mutant shows the major manifestations of the human disease: hypertyrosinemia, renal tubular damage and liver fibrosis and cirrhosis; Cas9n-mediated genome editing was used to correct the defect [182, 183]
 HPS model: Ruby/Red eye dilution (platelet storage disease) Rab38*
1, 152.07 Mb
HPS Direct sequencing of the gene; same mutation in FH and TM rats, probably derived from a common ancestor; lung surfactant secretion is altered in the mutant rats; Rab38 also controls proteinuria (QTL Rf2; see below) [184, 185]
 Hydrocephalus Ccdc39T
2, 120.28 Mb
The SD KO mutant shows severe hydrocephalus with subarachnoid haemorrhage and inflammatory cell invasion into the perivascular space, as well as impaired glymphatic cerebrospinal fluid flow [186]
 Hydrocephalus Ccdc85cT
6, 132.11 Mb
The F344 KO mutant shows non-obstructive hydrocephalus, subcortical heterotopia and intracranial hemorrhage [187]
 Hydrocephalus, X-linked L1camT
Xq37,
156.90 Mb
X-linked hydrocephalus L1CAM
Xq28
The SD KO male mutant shows reductions in fractional anisotropy and axial diffusivity in the corpus callosum, external capsule, and internal capsule [188]
Hyperbilirubinemia Abcc2**,T
1, 263.55 Mb
Hyperbilirubinemia II / DJS ABCC2
10q24
Direct sequencing of the cDNA in the Eisai hyperbilirubinemic rat (EHBR) revealed a premature stop codon; the same approach in the TR rat showed a 1 bp deletion; alterations were found in drug pharmacokinetics in an SD KO mutant; mutations were then discovered in theABCC2gene of DJS patients [138, 189,190,191]
 Hyperbilirubinemia Slco1b2T
4, 175.81 Mb
Hyperbilirubinemia (Rotor type) SLCO1B3
12p12.2
The SD KO mutant shows increased levels of serum bilirubin and altered pharmacokinetic behavior of pravastatin, an SLCO1B2 substrate; it could be a good model of the human Rotor syndrome [192]
 Hyperbilirubinemia Ugt1a1***
9q35,
95.30 Mb
Hyperbilirubinemia, Crigler-Najjar syndrome UGT1A
2q37.1
Direct sequencing of cDNA showed that the Gunn rat has a frameshift mutation in the 3′ region of the gene; correction of the defect could be achieved with recombinant UGT1A adenoviruses [193, 194]
 Hypercholesterolemia ApoeT
1, 80.61 Mb
Familial APOE deficiency APOE
19q13.32
An SD KO mutant displays hypercholesterolemia, atherosclerosis, hepatic steatosis and decreased HDL-cholesterol levels; another mutant also shows adventitial immune infiltrates; an Apoe/Ldlr double KO mutant was also studied by Zhao et al. (2018) [195] [195,196,197]
 Hypercholesterol-emia LdlrENU, T
8, 22.75 Mb
Familial hypercholesterolemia LDLR
19p13.2
The F344 and SD mutants display hypercholesterolemia, hypertriglyceridemia, atherosclerosis, xanthomatosis; hepatic steatosis was also found in the SD mutant [195, 198, 199]
 Hypercholesterol-emia
 (diet-induced: ExHc rat)
Ppp4r3b**
14, 113.57 Mb
Positional identification of the gene, coupled with gene expression analyses; the gene is under-expressed in the ExHC rat and carries a strain-specific10 bp deletion leading to a premature stop codon [200]
 Hyperuricemia UoxT
2, 252.445 MB
No functional gene The SD KO mutant is viable (unlike the mouse KO) and shows elevated levels of serum uric acid, providing a good model for studying hyperuricemia and associated disorders [201]
 Hypodactyly (hd) Cntrob**
10q24,
55.90 Mb
Positional identification of the gene; the hd allele carries a retroviral insertion; centrobin thus controls both limb development and spermatogenesis [202]
 Hypohidrotic ectodermal dysplasia (swh) Edaradd**
17, 90.80 Mb
Hypohidrotic ectodermal dysplasia EDARADD 1q42.3 Positional identification of the gene, which shows a missense mutation in the sparse-and-wavy rat (swh); sparse hair and oligodontia in this mutant rat and in human patients [203]
 Hypomyelination Bace1T
8, 50.14 Mb
The SD KO mutant shows increased axon density and relatively thinner myelin sheaths around axons of the sciatic nerves; it also shows increased mortality [204]
 Hypothyroidism TshrT
6q31.2,
115.17 Mb
Congenital hypothyroidism TSHR
14q31.1
The SD KO mutant is infertile and shows the dwarf phenotype as well as suppression of the thyroid-specific genes; the phenotype can be reversed by levothyroxine [205]
 Hypotrichosis (hairlessness) Dsg4**
18, 12.06 Mb
Hypotrichosis
18q12.1
DSG4
18q12
Direct sequencing of the IC hairless rat gene, which shows a large deletion; same approach in the lanceolate hair (lah) rat revealed a missense mutation; positional identification of the mutant gene from an SHR congenic strain, which shows a premature termination codon [206,207,208]
 Immunodeficiency IghT
6q32, ~ 150 Mb
Two SD KO mutants show absence of Ig and B cells; transgenesis of human IG loci reconstitutes B cell development and leads to humanized Ig production [209, 210]
 Immunodeficiency (athymia: nude) Foxn1**, T
10, 65.62 Mb
Lack of thymus, anencephaly FOXN1
17q11.2
Following positional identification of the mouse gene, the homolog rat gene was found to be mutated in the nude strain, disrupting thymus development and hair growth; two induced Wistar mutants were generated: they show thymus deficiency and incomplete hairless [211,212,213]
 Immuno-deficiency PrkdcT
11q23,
89.29 Mb
Immuno-deficiency, granuloma, autoimmunity PRDKC
8q11.21
The F344 KO mutant shows severe combined immunodeficiency and growth retardation; this mutant was used to establish a model for preclinical testing of human neural precursor cells transplantation as a treatment of neonatal brain damages; a double KO mutant (Prkdc−/− and Il2rg−/−) was also generated; this double mutant shows abolishment of natural killer cells [214, 215]
 Immunodeficiency (SCID) Rag1T
3, 91.21 Mb
SCID RAG1
11p12
The LEW KO mutant shows lymphocyte depletion (and attenuation of hypertension and renal damage: see below, Polygenic traits, Blood pressure) [216]
 Immunodifficiency (SCID) Rag2T
3, 91.19 Mb
SCID RAG2
11p12
The SD KO rat lacks mature B and T cells and was shown to be a viable host for a range of xenograft studies [217]
 Immunodeficiency (SCID) Rag1T
3, 91.21 Mb
Rag2T
3, 91.19 Mb
Il2rgT
X, 71.17 Mb
The SD triple KO mutant shows impaired development of lymphoid organs, is severely immunodeficient with an absence of mature T, B, and NK cells and supports fast growth of patient-derived xenografts thus holding great potential to serve as a new model for oncology research [218]
 Immunodeficiency (X-SCID) Il2rgT
X, 71.17 Mb
X-SCID IL2RG
Xq13.1
Two KO mutants are available; they show severe combined immunodeficiency (absence of B and T lymphocytes and of NK cells); a double KO, deficient for both Il2rg and Rag1, was also described: see above [219, 220]
 Infertility (and cryptorchidism) Adamts16T
1, 36.47 Mb
The KO SS homozygous mutant exhibits cryptorchidism and is infertile; the gene also controls blood pressure (see below, Polygenic traits, Blood pressure) [221]
 Infertility (testicular feminization) Ar*
Xq22,
67.66 Mb
Testicular feminization AR
Xq12
Direct sequencing of the gene in a testicular feminized strain: a missense mutation was found in the steroid-binding domain of the androgen receptor [222]
 Infertility Bscl2ENU
1, 225.04 Mb
Congenital generalized lipodystrophy BSCL2
11q12.3
The male KO mutant is infertile and shows small testis and azoospermia (the female is fertile); the gene could be involved in male human fertility; see also below, Monogenic traits, Lipodystrophy and Polygenic traits, Brain development [223]
 Infertility Defb23T
3, 147.93 Mb
Defb26T
3, 147.98 Mb
Defb42T
15, 46.16 Mb
The male SD mutant with CRISPR/Cas9-mediated single Defb gene disruption has no obvious fertility phenotype but the multiple KO mutant (Defb23/26 or Defb23/26/42) is subfertile [224]
 Infertility (male pseudohermaphrodism: TF rat) Dhh**
7, 140.58 Mb
Gonadal dysgenesis DHH
12q13.12
Positional identification of the gene which shows a missense mutation in the TF rat; the mutation causes agenesis of Leydig cells and androgen deficiency [225]
 Infertility Esr1T
1q12,
41.19 Mb
Male and female SD KO rats are infertile and show gonadal pathologies; see also below, Polygenic traits, Metabolism [226]
 Infertility Esr2T
6q24.2,
99.16 Mb
Two SD KO mutants were generated; male mutants are fertile while female mutants are infertile (no ovulation); however male mutants exhibit prostatic glandular hyperplasia and changes in expression of genes involved in epithelial proliferation and benign tumor formation; in the female mutants, numerous granulosa cell genes are differentially expressed (including Kiss1) [227,228,229]
 Infertility Kiss1T
13, 50.53 Mb
The KO mutant (male and female) fails to show secretion of luteinising hormone and onset of puberty [230]
 Infertility Prdm14T
5, 5.51 Mb
The WI KO mutant (male and female) fails to generate primordial germ cells and consequently, is infertile [231]
 Infertility (ifm mutation) Sbf1**
7, 130.26 Mb
Charcot-Marie-Tooth disease type 4B3 SBF1
22q13.33
Positional identification of the gene, which shows a mutation at a splice site in the ifm mutant; homozygous males are infertile (azoospermia); females are normal [232]
 Infertility (tremor rat: TRM/Kyo, carrying the tm mutation) Spata22***
10q24,
59.89 Mb
Positional identification of a deletion spanning > 200 kb; the tm deletion causes infertility and absence-like seizure in both sexes; male infertility was complemented by Spata22 transgenesis [233]
 Kininogen deficiency (BN/Ka rat) Kng2**
11, 81.51 Mb
Direct sequencing of the cDNA from the BN/Ka rat revealed a missense mutation which impairs hepatic secretion of the protein; this defect may also render vascular tissue prone to aortic aneurysm formation [234, 235]
 Lipodystrophy, congenital generalized Bscl2ENU
1, 225.04 Mb
Congenital generalized lipodystrophy BSCL2
11q12.3
The KO mutant develops generalized lipodystrophy (lack of white adipose tissue), is glucose intolerant and shows elevated plasma triglyceride and concentrations; see also above: Infertility and below: Polygenic Traits, Brain development [223]
 Lipodystrophy, neuropathy Lpin1**
6, 41.80 Mb
Rhabdomyolysis Myoglobinuria Metabolic disease traits LPIN1 2p25.1 ENU-induced mutant isolated on the basis of the phenotype and positional identification of the gene; the murine gene is mutated in the fld mouse (showing adipocyte defects and demyelination) [236]
 Lymphopenia (T-cell) & IBD Themis**
1, 17.28 Mb
Positional identification of the gene, which shows a mutation in the BNm rat, impairing Treg function [237]
 Microcephaly (flathead rat) Cit**
12, 46.33 Mb
Microcephaly CIT
12q23.24
Positional identification of the gene, which shows a single base deletion in the mutant rat (fh/fh), generating a stop codon; cytokinesis is defective in neuronal progenitors; this mutation also leads to epilepsy (see above) [153, 238]
 Morphogenesis Lpar1ENU
5, 75.56 Mb
The Msh6 mutant shows craniofacial disorder and small size [239]
 mTORopathy Depdc5T
14, 83.09 Mb
Epilepsy DEPDC5
22q12.2-q12.3
The homozygous F344 KO rat dies in utero; the heterozygous KO rat displays cortical cytomegalic dysmorphic neurons and has altered cortical neuron excitability (upregulation of the mTORC1 pathway) [240]
 Mucopolysacchar-idosis VI Arsb***
2, 23.39 Mb
Mucopolysaccharidosis VI ARSB
5q11-q13
Direct sequencing of the Arsb cDNA showed a frame shift mutation with premature stop codon in affected rats (MPR); enzyme replacement therapy [241, 242]
 Multiple mitochondrial dysfunctions syndrome Isca1T
17, 5.28 Mb
Multiple mitochondrial dysfunctions syndrome ISCA1 The heterozygous SD KO mutant is normal but the homozygous mutant shows abnormal development at 8.5 days and dies at embryonic stage [243]
 Myogenic response Dusp5T
1, 274.25 Mb
The FHH.1BN congenic KO mutant shows greater myogenic response of cerebral arteries and enhanced autoregulation of cerebral blood flow [244]
 Neurological disorder (frogleg mutation) Bckdk**
1, 199.35 Mb
Autism and epilepsy BCKDK
16p11.2
Positional identification of the gene which shows a critical missense mutation in the frogleg rat, causing abnormalities in hind limb function, reduced brain weight, infertility, seizures [245]
 Neuropathy (Chemotherapy-induced peripheral neuropathy) C3T
9, 9.72 Mb
C3 is activated by neuronal cells in WT rats after paclitaxel administration; the KO mutant rat has reduced intradermal nerve fiber loss and mechanical allodynia after paclitaxel treatment [246]
 NGLY1-deficicency model Ngly1T
15, 10.40 Mb
NGLY1-deficiency NGLY1
3p24.2
The SD KO mutant shows developmental delay, movement disorder, somatosensory impairment, axonal degradation in the sciatic nerves and scoliosis, in agreement with the symptoms of human patients [247]
 Obesity Cdkn1b*
4, 168.69 Mb
Multiple endocrine neoplasia type 4 CDKN1B
12p13.1
The MNX (SDwe) rat is mutated in the Cdkn1b gene and shows multiple endocrine neoplasia syndrome; this mutant produces elevated levels of ghrelin and shows increased food intake with enhanced body fat mass; see also above, Cancer, Multiple endocrine neoplasia-like syndrome X and below, Polygenic traits, Cancer, Mammary gland development [248]
 Obesity LepT
4, 56.34 Mb
Obesity LEP
7q31
Targeted and ENU-induced mutations; F344 and SD KO rats are obese, infertile and immunodepressed [249, 250]
 Obesity Lepr**,T
5, 120.50 Mb
Obesity LEPR
1p31
Positional identification of the gene; missense or stop mutation in the Zucker fa and Koletsky obese (“corpulent”) rats, respectively; the SD KO mutant confirms the phenotype of the spontaneous mutant, with glucose intolerance, hyperinsulinemia, dyslipidemia and diabetes complications [251,252,253]
 Obesity Mc4rENU
18, 62.61 Mb
Obesity MC4R
18q22
The MSH6 KO mutant shows increased food intake and adipose mass [254]
 Osteochondrodysplasia (ocd) Golgb1**
11, 66.76 Mb
Positional identification of the gene; the mutant shows an abnormal skeletal system and systemic edema [255]
Osteopetrosis (incisors absent:ia) Plekhm1**
10, 91.45 Mb
Osteopetrosis PLEKHM1
17q21.31
Positional identification of the gene: frameshift mutation in theiarat; mutations discovered in thePLEKHM1gene of osteopetrosis patients [256]
 Osteoporosis pseudoglioma model Lrp5T
1, 218.82 Mb
Osteoporosis pseudoglioma LRP5
11q13.2
Three independent SD KO lines were generated: they display decreased trabecular bone mass and quality as well as sparse and disorganized superficial retinal vasculature as seen in LRP5-deficient humans [257]
 Parkinson disease model Lrrk2T
7, 132.86 Mb
Familial PD (dominant) LRRK2
12q12
The Long Evans KO mutant displays weight gain and an abnormal kidney, lung and liver phenotype [258, 259]
 Parkinson disease model Nr4a1ENU
7, 142.90 Mb
The FHH KO mutant shows reduced dopamine cell loss and dyskinesia in this experimental Parkinson disease model; the gene also controls renal function and stress: see below, Polygenic traits, Renal injury and Behavior, stress response [260]
 Parkinson disease model Park7T
5, 167.98 Mb
Familial PD (recessive) PARK7 1p36.23 The Long Evans KO mutant shows motor deficit and age-dependent neuronal loss; Park7 is also involved in the control of PAH: see below, Polygenic traits, Blood pressure [261, 262]
 Parkinson disease model PrknT
1, 48.88 Mb
Familial PD (recessive) PRKN
6q26
The Long Evans KO mutant is not different from WT rats [262]
 Parkinson disease model Pink1T
5, 156.68 Mb
Familial PD (recessive) PINK1
1p36
The Long Evans KO mutant shows motor deficit and age-dependent loss of nigral dopaminergic neuronal [261,262,263]
 Parkinson disease model Snca*
4, 90.78 Mb
Familial PD (dominant) SNCA
4q22.1
Direct sequencing revealed a mutation in the Snca mRNA 3’UTR in a mutant rat, which overexpresses synuclein alpha and shows functional alterations in the dopaminergic and glutamatergic systems [264, 265]
 Phelan-McDermid syndrome model Shank3T
7, 130.47 Mb
Phelan-McDermid syndrome SHANK3
22q13.33
The human neurobehavioral manifestations are due to mutations in SHANK3; one of these mutations (a deletion) was introduced in rats, which exhibited disabilities related to those seen in the human patients; these deficits were attenuated by oxytocin treatment [42]
 Pinked eyed dilution (p) Oca2**
1, 114.66 Mb
Oculocutaneous albinism OCA2
15q
Direct sequencing of the Oca2 cDNA revealed a deletion shared by several mutant strains, that also exhibit the same haplotype, distinct from control strains [266]
 Polycystic kidney disease (ADPKD) (cy/+ rat) Anks6***
5, 62.64 Mb
Cystic kidney disease (Nephronophthisis) ANKS6 Positional identification of the gene, mutated in the Han SD (cy/+) rat; overexpression of the mutated variant causes polycystic kidney disease; mutations later found in the human gene [267,268,269]
 Polycystic kidney disease (ARPKD): nephronophtisis Nek8**
10, 65.40 Mb
Positional identification of the gene, mutated in the Lewis Polycystic Kidney (LPK) rat, leading to abnormally long cilia on kidney epithelial cells [270]
 Polycystic kidney disease (ARPKD) P2rx7T
12, 39.35 Mb
A P2rx7 KO was generated in the polycystic kidney (PCK) rat, a model of ARPKD; the mutant shows slower cyst growth and reduction of renal pannexin-1 protein expression and daily urinary ATP excretion [271]
Polycystic kidney disease (ARPKD) Pkhd1**
9, 26.16 Mb
ARPKD PKHD1
6p12.2
Positional identification of the polycystic kidney (PCK) rat gene, which led to the identification of mutations in the homolog human gene, responsible for ARPKD [272]
Polycystic kidney disease (Wpk rat) Tmem67**
5, 27.67 Mb
Meckel-Gruber syndrome (MKS3) TMEM678q24 Positional identification of the rat gene, which led to the identification of mutations in the human gene responsible for MKS3; central nervous system defects are also present in humans and rats [273]
 Polydactyly (Lx) Zbtb16**,T
8, 52.99 Mb
Skeletal defects and genital hypoplasia ZBTB16
11q23.2
Positional identification of the gene which shows a 2.9 kb deletion in the Lx intron 3 and is down-regulated; the heterozygous SHR KO mutant shows anomalies in the caudal part of the body (caudal regression) and growth retardation (the homozygous KO is lethal) [274, 275]
 Pseudoxanthoma elasticum Abcc6T
1, 101.95 Mb
Pseudoxantho-ma elasticum ABCC6
16p13.11
This mineralization disorder is associated with reduced plasma inorganic pyrophosphate; this study of the SD KO mutant points to a critical role of liver ABCC6 [276]
 Reed syndrome FhT
13, 93.65 Mb
Reed syndrome FH
1q43
The SD heterozygous KO mutant shows hematopoietic and kidney dysfunction with kidney anaplastic lesions [277]
 Retinal dystrophy (Rdy) (RCS rat) Mertk***
3, 121.24 Mb
Retinitis pigmentosa (autosomal recessive) MERTK 2q14.1 Positional identification of the gene: small deletion in the RCS rat, the defect of which could be corrected by gene transfer [278,279,280]
 Retinal telangiectasia (BN-J rat) Crb1**
13, 56.27 Mb
Retinal dystrophies (including telangiectasia) CRB1
1q31.3
The BN-J rat shows several retinal abnormalities reminiscent of human macular telangiectasia; sequencing of the BN-J and BN exons revealed the presence of a rearrangement in exon 6 of BN-J, which segregates with the phenotype in an F2 cross [281]
 Retinitis pigmentosa Pde6bT
14, 2.33 Mb
Retinitis pigmentosa (autosomal recessive) PDE6B
4p16.3
The SD KO mutant exhibits photoreceptor degeneration, profound retinal thinning and extensive degeneration of the outer nuclear layer [282]
 Rett syndrome Mecp2T
X, 156.65 Mb
Rett syndrome MECP2
Xq28
The SD KO mutant shows early motor and breathing abnormalities, growth retardation, malocclusion, reduction of brain weight [283,284,285]
 Rickets model (type 1A) Cyp27b1T
7, 70.33 Mb
Type 1A rickets CYP27B1
12q14.1
The Wistar KO mutant shows growth failure and rickets; administration of 25-Hydroxyvitamin D3 results in normalization of most phenotypes, including osteogenesis [286]
 Rickets model (type 2A) VdrT
7q36,
139.34 Mb
Type 2A rickets VDR
12q13.11
The Wistar KO mutant shows growth failure and rickets, with alopecia; a mutant containing the human mutation R270L was also isolated: it also shows rickets symptoms, reversed by 25-Hydroxyvitamin D3 administration; with the above mutant, these 2 mutants could be useful to study the effects of vitamin D derivatives [286]
 Sitosterolemia Abcg5**
6q12, 7.94 Mb
Sitosterolemia ABCG5/
ABCG8
2p21
Positional identification of the gene; same missense mutation in SHR, SHRSP and WKY, exhibiting elevated plant sterol accumulation [287]
 Small eye (rSey): microphthalmia Pax6*
3, 95.70 Mb
Aniridia, mental retardation, autism PAX6
11p13
Direct sequencing of the mutant cDNA, which shows a 0.6 kb deletion; impaired migration of neural crest cells; the mutant rat may have some phenotypic component of autism [288, 289]
 Spondylocostal dysostosis (Oune mutation) Tbx6**
1, 198.21 Mb
Spondylocostal dysostosis TBX6
16p11.2
ENU-induced semi-dominant mutation, causing a short and kinked tail and several skeletal abnormalities; positional identification of the mutant gene [290]
 Tenogenesis MkxT
17, 60.54 Mb
The Wistar KO mutant shows heterotopic ossification of the Achilles tendon via failed tenogenesis [291]
 Teratoma and infertility (ter) in both sexes Dnd1**
18, 29.61 Mb
Positional identification of the gene: premature stop codon in WKY/Ztm rats; homologous to the mouse mutation Ter (which induces testicular teratomas only) [292]
 Testicular feminization (Tfm) Ar*
Xq22,
67.66 Mb
Testicular feminization AR
Xq12
Direct sequencing of cDNA: single base alteration in the Ar gene leads to androgen insensitivity and lack of male sexual development [222]
 T-helper immuno-deficiency (thid) Ptprk**
1, 17.44 Mb
Positional identification of the gene: large deletion in LEC rats, the phenotype of which could be rescued by reconstitution with normal bone marrow cells [293, 294]
 Toothless (tl), osteopetrosis Csf1**
2, 210.52 Mb
Positional identification of the gene: early stop codon in the tl Csf1 gene; similar to the mouse op; see below, Polygenic traits, Macrophage development for Csf1r KO rats [295, 296]
 Toxicity: aflatoxin B1 toxicity Nfe2l2T
3, 62.50 Mb
The F344 KO mutant is highly sensitive to aflatoxin B1 toxicity, due to impaired capacity for detoxification; Nfe2l2 also controls vasculature function: see below [297]
 Toxicity: anthrax toxin susceptibility Nlrp1**
10q24,
57.69 Mb
Susceptibility maps in the region of Nlrp1 (in recombinant inbred strains) and gene polymorphism is correlated with susceptibility in several rat strains; the gene also controls Toxoplasma susceptibility: see below [298]
 Toxoplasma susceptibility (Toxo1) Nlrp1***
10q24,
57.69 Mb
Toxoplasmosis susceptibility NLRP1
17p13.2
Positional identification of the gene; KO of Nlrp1 in macrophages modifies Toxoplasma replication; in humans, association between NLRP1 polymorphism and toxoplasmosis susceptibility; the gene also controls sensitivity to anthrax toxin: see above [299]
 Tremor (tremor rat: TRM/Kyo, carrying the tm mutation) Aspa*,T
10, 59.84 Mb
Canavan disease ASPA
17p13.2
Positional identification of a deletion spanning > 200 kb in the TRM/Kyo rat; injection of N-acetyl-L-aspartate, the Aspa precursor, induces absence-like seizure in normal rats (the tremor rat exhibits absence-like seizure); an F344 KO mutant shows abnormal myelination but no tremor; however an Aspa/Hcn1 double mutant shows tremor, like the TRM/Kyo rat, which is a double mutant (see below, Polygenic traits, Epilepsy, tremor, Hcn1); the pathogenesis of tremor involves ionotropic glutamate receptors [124, 300, 301]
 Tremor: Zitter rat (zi mutation) Atrn***
3q35,
123.43 Mb
zi induces hypomyelination and vacuolation in the CNS; positional identification of the gene; zi is homologous to the mouse mg (mahogany); complementation by transgenic membrane-type Atrn [302, 303]
 Tremor: VF rat (vf mutation) Dopey1**
8, 94.12 Mb
vf induces hypomyelination and vacuolation in the CNS; positional identification of the gene, which carries a nonsense mutation [304]
 Tremor (Trdk mutation) Kcnn2**
18, 39.33 Mb
ENU-induced missense mutation; positional identification of the mutant gene [305]
 Unilateral renal agenesis (URA; Renag1) Kit***
14, 37.07 Mb
ACI rats exhibit URA and white spotting; positional identification of the gene, which carries an insertion; removing the insertion by the CRISPR/Cas9 system corrects the disease and the white spotting phenotype; Kit also controls the hooded phenotype: see above, Coat color; the gene may also control anemia (see above) [306, 307]
 Warfarin resistance (rw) Vkorc1** 1, 199.34 Mb VKCFD2 and warfarin resistance VKORC1
16p11.2
Positional identification of the gene, mutated in warfarin resistance (humans and rats) and VKCFD2 (humans) [308, 309]
 Wilson disease model Atp7b**
16q12,
74.87 Mb
Wilson disease ATP7B
13q14.3
Positional identification of the gene: deletion in the LEC rat gene, causing hepatitis [310, 311]
 Wolfram disease model Wfs1T
14, 78.64 Mb
Wolfram disease WFS1
4p16.1
The SD KO mutant shows the core symptoms of the human disease: diabetes mellitus, glycosuria, neurodegeneration; treatment with a GLP1 receptor agonist prevents the development of diabetic phenotype in the KO rat [312, 313]
 Wolman disease model (Wolman rat) Lipa*
1, 252.82 Mb
Wolman disease LIPA
10q23
Direct sequencing of the mutant rat cDNA: deletion of the Lipa gene in the Wolman rat [314]
B) Polygenic traits (QTL symbol)
 Addiction: alcohol consumption Adcyap1r1*
4, 85.66 Mb
Alcohol consumption in women ADCYAP1R1
7p14.3
(Association study)
Positional identification of the gene and expression studies in congenic strains; the trait is female-specific; Adcyap1r1 is upregulated in alcohol-preferring females and its promoter contains several ERE’s and polymorphisms associated with a differential response to estrogen stimulation in vitro [315]
 Addiction: alcohol consumption Grm2*
8, 115.34 Mb
Positional identification of the gene; stop codon in the alcohol-preferring rat strain allele; (see also above, Monogenic traits, Addiction; opioid consumption); however, this conclusion was challenged on the basis of experiments showing that a lentiviral-delivered short-hairpin RNA-mediated KO of Grm2 does not promote alcohol drinking [316,317,318]
 Addiction: alcohol consumption (Alc22) Crhr2*
4, 85.29 Mb
Polymorphisms in the promoter, coding region, and
3’UTR were associated with altered CRHR2 binding density in alcohol-preferring rat strain (no mapping of the trait)
[319]
 Addiction: alcohol consumption (Alc11/13) Cyp4f18**
16, 19.50 Mb
DNA sequencing of rats from HS-derived high- and low-alcohol-drinking lines revealed several genomic regions showing signature of selection, including genes located in previously identified QTLsd [320]
 Addiction: alcohol consumption (Alc11/13) Fam129c**
16, 20.03 Mb
See comment above, on Cyp4f18 [320]
 Addiction: alcohol consumption (Alc5/9/12) Grin2a**
10q11,
5.71 Mb
See comment above, on Cyp4f18 [320]
 Addiction: alcohol consumption (Alc11/13) Myo9b**
16, 19.67 Mb
See comment above, on Cyp4f18 [320]
 Addiction: alcohol consumption NpyT
4, 79.56 Mb
Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight [321]
 Addiction: alcohol consumption (Alc11/13) Pgls**
16, 20.02 Mb
See comment above, on Cyp4f18 [320]
 Adiposity Angptl8T
8, 22.86 Mb
The F344 KO mutant shows lower body weight, lower fat content and lower triglyceride levels, but higher heart lipase levels than WT rats [322]
 Allergic rhinitis Muc1T
2, 188.54 Mb
The SD KO rat shows aggravation of allergic rhinitis and suppression of expression of epithelial cell connection proteins [323]
 Angiogenesis Agtr1aT
17q12,
35.90 Mb
The SS KO rat shows no response to injection of angiotensin II (as expected) and no increase in hind limb vessel density upon angiotensin-(1–7) infusion (the effects of which are mediated by Mas1), indicating an AGTR1A-MAS1 interaction; the gene also controls Blood pressure (see below) [324]
 Angiogenesis Wars2**, T
2q34,
201.17 Mb
Cardio-metabolic phenotypes WARS2
1p12
Positional identification of the gene controlling coronary flow; the BN KO mutant shows diminished cardiac capillary density and reduced coronary flow; the gene also controls the metabolic syndrome: see below [325]
 Aorta elastic tissue integrity (Vetf3) Pi15**
5, 0.79 Mb
High resolution mapping in a HS; lower expression of Pi15 in the susceptible strain BN (combined with higher expression of a long intergenic noncoding RNA) [326]
Arthritis CIIta**
10, 5.21 Mb
RA, MS, myocardial infarction CIITA
16p13
Positional identification of the rat gene, definitively identified by sequencing and expression analysis; in humans, polymorphism in the promoter was associated with disease susceptibility [327]
Arthritis
(Pia7, Oia2)
Clec4b**
4q42,
156.11 Mb
RA CLEC4A
12p13
Positional identification of theAplecrat gene complex and then of theClec4bgene; association was found between RA andCLEC4A(=DCIR) in human patients [328,329,330,331]
 Arthriris Fcgr1aT
2, 198.43 Mb
A conditional SD KO rat was generated in which the gene was inactivated in the dorsal root ganglion; the rat shows attenuation of pain upon antigen-induced arthritis, indicating that neuronal FCGR1A contributes to arthritic pain [332]
 Arthritis Git2T
12, 47.59 Mb
The SD KO rat with induced arthritis shows a more severe disease, with decreased collagen II expression and increased expression of inflammatory cytokines [333]
 Arthritis: gout P2ry14T
2, 149.33 Mb
The SD KO rat shows disruption of urate-induced histopathologic changes in rat synoviums, accompanied with a significant inhibition of pyroptotic macrophage death [334]
 Arthritis: PIA Hip1**
12q16,
24.18 Mb
Positional identification of the gene, which is required for the increased invasiveness of synoviocytes from arthritic rats and from RA patients [335]
 Arthritis (Pia8) Il22ra2**    See Eae29  
Arthritis (Pia4) Ncf1**
12, 25.50 Mb
RA NCF4
22q13.1
Positional identification of the gene and of the causative mutation; the gene controls the production of reactive oxygen species; see also below: Experimental autoimmune neuritis [43, 330, 336, 337]
 Arthritis: PIA Lta, Ltb, Tnf, Lst1, Ncr3**
20p12,
3.65–3.71 Mb
Positional identification of a recombination-resistant 33 kb segment, made of 5 genes, within the MHCIII region; one conserved haplotype regulates arthritis; haplotype-specific differences in gene expression and alternative splicing correlate with susceptibility to arthritis; the haplotype specifically regulates adjuvant-induced arthritis, but not antigen-induced autoimmunity [338, 339]
 Arthritis: Pia1 RT1-Ba**
20p12,
4.07 Mb and RT1-Bb**
20p12,
4.04 Mb
RA MHCII
6p21.32
Using a mixed genetic and functional approach, these 2 genes (orthologs of the human HLA-DQA and HLA-DQB loci, in the MHCII region) were shown to control the onset and severity of PIA [340]
Arthritis: PIA Vav1**
9q12, 9.62 Mb
RA VAV1
19p13.2
Polymorphism inVav1controls PIA in the rat; in humans,VAV1SNPs are associated with RA; see also below,Eae4 [341]
 Asthma Trpa1T
5, 3.78 Mb
The SD KO rat is largely protected from immune cell infltration into bronchoalveolar lung fuid in the ovalbumin model of asthma; on the other hand, it shows normal behavioral responses in multiple models of pain and itch [342]
 Behavior Cplx1T
14, 2.20 Mb
The SD KO mutant shows severe ataxias and tremor, dystonia, uncoordinated locomotion, exploratory deficits, anxious behavior and sensory deficits as well as decreased dendritic branching in spinal motor neurons [343]
 Behavior Phf24T
5, 58.36 Mb
The F344 KO mutant shows no apparent changes in gross behaviors during adolescence but, at older age, it exhibits elevated spontaneous locomotor activity, emotional hyper-reactivity, reduced anxiety behaviors and cognitive deficits; it also shows a higher sensitivity to induced convulsive seizures [344]
 Behavior: Attention-deficit hyperactivity disorde rmodel Adgrl3T
14, 28.36 Mb
Attention-deficit hyperactivity disorder ADGRL3
4q13.1
The SD KO mutant shows persistent hyperactivity, increased acoustic startle, reduced activity in response to amphetamine and female-specific reduced anxiety-like behavior; dopamine signaling is dysregulated in the neostriatum [345, 346]
 Behavior: aggressive phenotype Tph2T
7, 58.04 Mb
The DA KO mutant exhibits (as expected) profoundly diminished serotonin level and displays increased aggressiveness [347]
 Behavior: anxiety Cckar*
14, 59.61 Mb
Gene deletion in the OLETF rat; no mapping of the trait; see also below, Body temperature and Diabetes, type 2 [348]
Behavior: anxiety, depression Ctnnd2**
2, 83.39 Mb
Schizophrenia, Depressive disorder CTNND2
5p15.2
Positional identification of the rat gene; the human gene was then associated with schizophrenia and major depressive disorder [28, 349, 350]
 Behavior: anxiety, depression Slc6a4ENU
10, 63.15 Mb
Anxiety/ depression SLC6A4
17q11.2
The Wistar KO mutant lacking the serotonin transporter shows anxiety, depression-related behavior and impaired object memory as well as alterations in DNA methylation of the urocortin promoter [351, 352]
 Behavior: anxiety, drug addiction Oprl1ENU
3, 177.23 Mb
The Wistar KO mutant lacking the nociceptin/orphanin FQ receptor rat shows an anxiety-like phenotype and is more sensitive to the rewarding effect of morphin [353, 354]
 Behavior: autism-like symptoms Nrxn1T
6, 14.75 Mb
Autism NRXN1
2p16
The SD KO mutant shows persistent nonsocial deficits, including hyperactivity, deficits in simple instrumental learning, latent inhibition, and spatial-dependent learning [355]
 Behavior: dopamine-related brain disorders Drd1ENU
17, 11.10 Mb
The Wistar mutant carries a missense mutation that leads to a decreased transmembrane insertion of DRD1; it displays normal basic neurological parameters and locomotor activity but reduced social cognition (such as social interaction) [356]
 Behavior: dopamine-related brain disorders Slc6a3ENU,T
1, 32.32 Mb
Several psychiatric disorders Two mutants are available: an F344 ENU-induced missense mutant and a targeted Wistar KO mutant; both strains show locomotor hyperactivity and impaired cognitive processes; they are excellent models for the evaluation of the effects of novel therapeutics on cognitive functions linked to the dopamine transporter [357, 358]
 Behavior: drug addiction (cocaine) Trpc4T
2, 143.43 Mb
The F344 KO mutant shows reduced acquisition of cocaine self-administration compared to WT rats; see also below: Blood pressure -PAH- and Behavior, drug addiction [359]
 Behavior: fear memory CrebbpT
10, 11.59 Mb
An SD mutant was generated using a novel method that targets the Crebbp gene in a population of neurons of the medial prefrontal cortex; the mutant shows impaired fear (remote) memory and impaired extinction learning [360]
 Behavior: fear memory Rin1T
1, 220.33 Mb
The SD KO mutant shows a deficit in the formation and extinction of auditory fear memory, associated with enhanced apoptosis in the hippocampus [361]
 Behavior: fear memory and coping Nr3c1T
18p12,
31.73 Mb
A conditional SD KO mutant was generated, targeting output neurons and the prelimbic cortex; females exhibit deficits in acquisition and extinction of fear memory; males exhibit enhanced active-coping behavior during forced swim [362]
 Behavior: mental illnesses Disc1T
19, 57.82 Mb
Mental illnsesses DISC1
1q41.2
The SD mutant shows changes in white matter microstructural integrity and deficits in neurite density (it recapitulates many of the neuroimaging findings seen in populations of schizophrenia); the male is more affected than the female mutant [363]
 Behavior: neuropsychiatric disorders model Cacna1cT
4, 150.64 Mb
Autism, bipolar disorder, schizophrenia CACNA1C
12p13.33
The heterozygous SD KO mutant shows deficits in social behavior and in pro-social ultrasonic communication; however this haploinsufficiency has a minor positive impact on memory functions [364, 365]
 Behavior: neuropsychiatric disorders and PCH3 model PcloT
4, 16.45 Mb
Psychiatric and developmental disorders and PCH3 PCLO
7q21.11
(GWAS)
The SD KO mutant shows a reduction in the number of synaptic vesicles, which show abnormal recycling, deficient formation of early endosomes and altered synaptic transmission; the mutant displays impaired motor coordination [366, 367]
 Behavior: stress response Dpp4T
3, 48.29 Mb
The DA.F344 KO congenic mutant is stress-resilient and shows decreased expression of Nr3c1 and Fkbp5 in the amygdala and the hypothalamus as well as lower stress-induced peripheral corticosterone levels [368]
 Behavior: stress response Nr4a1T
7, 142.90 Mb
The male FHH KO mutant was only used to study gene expression in the prefrontal cortex; the mutant shows reduced expression of the AMP-activated protein kinase, indicating that NR4A1 favors the adverse effects of stress; the gene also controls Parkinson disease (see above) and Renal injury (see below) [369]
 Behavior: stress response Nrg1T
16, 62.97 Mb
Schizophrenia NRG1
8p12
The F344 KO mutant shows alterations in HPA axis activity and behavioral responses to stress [370]
 Behavior: stress response (Stresp24) Stim1**
1, 167.37 Mb
Autoimmunity STIM1
11p15.4
Positional identification of the gene; nonsense mutation in several SHRSP substrain alleles, absent in WKY and other normotensive strains; this mutation impairs Ca++ signaling in astrocytes; this pleiotropic genes also controls Diabetes insipidus (see above), Renal injury and Stroke (see below) [371, 372]
 Bladder function Trpv4T
12, 47.70 Mb
The phenotype of the SD KO mutant shows that in a model of underactive bladder, intravesical activation of TRPV4 improves bladder function [373]
 Blood pressure Agtr1aT
17q12,
35.91 Mb
The MSH6 KO mutant shows an extremely high blood pressure-like phenotype; the gene also controls Angiogenesis (see above) [239]
Blood pressure:BpQTL2 Adamts16**,T
1, 36.47 Mb
Hypertension ADAMTS165p15 Positional identification of the gene, which shows exonic variants; association between ADAMTS16 and blood pressure was then discovered in humans; KO of the gene in the SS rat leads to lower blood pressure; this gene also controls male fertility: see above, Monogenic traits, Infertility [374, 375]
Blood pressure Add1**
14, 82.06 Mb
Hypertension and CV risks ADD1
4p16.3
Positional identification of the gene: missense polymorphisms in the Milan Hypertensive Rat and in humans; in vitro functional studies [376, 377]
Blood pressure:Bp77 Arntl**
1, 171.06 Mb
Hypertension and NIDDM ARNTL
11p15
Functional polymorphisms found in the rat gene promoter; association was then established in the human with blood pressure and type 2 diabetes [378]
 Blood pressure Cd247T
13q23,
88.88 Mb
Hypertension 1q24 locus (GPA33, CD247, F5, REN) The SS KO mutant exhibits reduced kidney infiltration of T cells, mean arterial blood pressure and kidney damage [379, 380]
 Blood pressure Cd36**
4, 14.15 Mb
Positional identification of the gene, combined with gene expression studies; deficient renal expression of Cd36 (in SHR) is a genetically determined risk factor for spontaneous hypertension; the gene also controls diabetes: see below [29]
 Blood pressure
 (C17QTL1)
Chrm3**,T
17q12,
63.99 Mb
Positional identification of the gene; the SS rat carries a missense mutation enhancing receptor activity; the KO SS mutant exhibits lower salt-induced hypertension and improved renal function [381]
 Blood pressure Chst12**
12, 18.19 Mb
Hypertension 7p22 Positional identification of the gene; the SS allele contains mutations when compared with several normotensive strains; this rat region is homologous to a region on human chromosome 7 that has been linked to blood pressure [382]
 Blood pressure Clcn6T
5, 168.47 Mb
Hypertension AGTRAP-PLOD1 locus; 1p36 The SS KO mutant shows decreased blood pressure; the human locus was identified in GWAS and CLCN6 could be linked to blood pressure and renal phenotypes [39]
 Blood pressure Cyp11b1**
7, 112.98 Mb
Positional identification of the gene; the characteristic steroid profiles of SS and SR rats can be explained by the biochemical properties of CYP11B1; 5 mutations found in the SS allele, segregating with blood pressure and altered steroid biosynthesis in a SS X SR cross [383]
 Blood pressure Cyp17a1**
1q55, 266.42 Mb
Hypertension CYP17A1
10q24.32
Extensive proteomics and transcriptome studies in the BN and SHR strains led to the discovery that Cyp17a1 is downregulated in SHR, probably as a consequence of a promoter mutation; in humans a SNP in CYP17A1 was associated with hypertension [384]
 Blood pressure Gja8**
2, 199.05 Mb
The Gja8 mutation present in the SHR-Dca strain (causing cataract; see above, Monogenic traits) lowers blood pressure and decreases high density lipoprotein cholesterol concentration [385]
 Blood pressure Gper1T
12, 17.31 Mb
The SS KO mutant presents with lower blood pressure, accompanied by altered microbiota and improved vascular relaxation [386]
 Blood pressure Hsd11b2T
19q12,
37.48 Mb
SAME HSD11B2
16q22.1
The F344 KO mutant exhibits hypertension, hypokalemia, renal injury; the phenotype closely models the human SAME [387]
 Blood pressure Htr7T
1, 254. 55 Mb
Unlike wild-type rats, the SD KO mutant does not show reduced mean arterial pressure nor splanchnic venodilation upon serotonin infusion [388]
 Blood pressure Kcnj1T
8, 33.45 Mb
Type II Bartter syndrome KCNJ1
11q24
The SS KO mutant exhibits protection from salt-induced blood pressure elevation [389]
 Blood pressure Kcnj16T
10, 99.33 Mb
Brugada syndrome (arrhythmias) KCNJ16
17q24.3
The SS KO mutant exhibits hypokalemia and reduced blood pressure; when fed on a high salt diet, this mutant dies as a result of salt wasting and severe hypokalemia; the gene also controls pH homeostasis: see above, Monogenic traits, Acidosis [390]
 Blood pressure Ncf2***,T
13, 75.2 Mb
Positional identification of the gene, which shows higher expression and promoter mutation in the SS rat; disruption of the gene reduces hypertension and renal oxidative stress and injury; Ncf2 is involved in luminal flow-mediated O2·− production (i.e. oxidative stress) [391, 392]
 Blood pressure Nox4T
1, 150.80 Mb
The SS KO mutant shows reduction of salt-induced hypertension and of albuminuria compared with the wild-type SS rat; Nox4 contributes to the production of H202 (i.e. oxidative stress) [392, 393]
 Blood pressure NppaT
5q36,
165.81 Mb
Hypertension AGTRAP-PLOD1 locus; 1p36 The SS KO mutant shows increased blood pressure; the human locus had been identified in GWAS and NPPA could be linked to blood pressure phenotypes [39]
 Blood pressure NppbT
5q36,
164.79 Mb
Hypertension and left ventricular dysfunction NPPB
1p36.22
The SS KO mutant shows adult-onset hypertension, left ventricular hypertrophy and increased cardiac stiffness [394]
 Blood pressure Nr2f2T
1, 131.45 Mb
Hypertension NR2F2
15q26
NR2F2 was associated with hypertension in humans; an hypomorphic SS mutant shows lower systolic and diastolic blood pressures [395]
 Blood pressure Pappa2**
13, 36.39 Mb
Positional identification of the gene (including generation of SS subcongenic strains); renal cortex Pappa2 mRNA level is lower in the SS rat [396]
 Blood pressure (HTNB) Pde3aT
4, 175.43 Mb
Hypertension (HTNB) PDE3A
12p12.2
An SD mutant carrying a 9 bp deletion similar to that found in a human patient is hypertensive and recapitulates HTNB (including shorter fingers); the mutation causes an increase in enzyme activity with peripheral vascular resistance; the data suggest that soluble guanylyl cyclase activation could be suitable for the treatment of HTNB patients [46]
 Blood pressure Plekha7T
1, 185.43 Mb
Hypertension PLEKHA7
11p15.1
PLEKHA7 is a candidate gene for human hypertension; the SS KO mutant shows attenuated salt-sensitive hypertension and vascular improvements [397]
 Blood pressure Plod1T
5, 168.38 Mb
Hypertension AGTRAP-PLOD1 locus 1p36 The SS KO mutant shows increased systolic blood pressure; the human locus was identified in GWAS [39]
 Blood pressure Prdx2T
19, 26.08 Mb
The SHR KO mutant exhibits shorter life span and modest blood pressure increase via increased oxidative stress [398]
 Blood pressure Rag1T
3, 97.87 Mb
SCID RAG1
11p13
The SS KO mutant exhibits attenuation of blood pressure and of renal damage (and lymphocyte depletion: see above, Monogenic traits, Immunodeficiency) [399]
 Blood pressure Rarres2T
4, 78.21 Mb
The SD KO female mutant (but not the KO male) exhibits a relative resistance to hypertension in response to a hypertensive challenge [400]
 Blood pressure RenT
13q13,
55.55 Mb
The SS KO mutant shows a greatly reduced blood pressure, changes in kidney morphology and reduced adrenal synthesis of aldosterone and Cyp11b2 [401, 402]
 Blood pressure Resp18T
9, 82.47 Mb
The SS KO mutant shows increased systolic and diastolic blood pressure, as well as increased renal damage (Resp18 is located in a blood pressure QTL) [403]
 Blood pressure Sh2b3T
12, 40.26 Mb
Hypertension SH2B3
12q24
SH2B3 has been associated with hypertension; in the SS KO mutant, hypertension and renal disease are attenuated via inflammatory modulation; the gene also controls cardiac inflammation: see above, Monogenic traits [404]
 Blood pressure Sry1*
Y
Hypertension ?
Y
Delivery of Sry1 cDNA to the kidney increases blood pressure in normotensive WKY rats [405]
 Blood pressure Zbtb16**T
8, 51.57 Mb
Positional identification of the gene in RI strains and in an SHR-PD congenic; deletion in the intron 2 of the PD allele, which is down-regulated and is protective; the heterozygous SHR KO mutant shows no change in blood pressure (the homozygous KO is lethal) [406, 407]
 Blood pressure: captopril effects Ednrb**
15q22,
88.00 Mb
The antihypertensive effects of the ACE inhibitor captopril behave as a polygenic trait in RI strains; Ednrb was positionally identified: correlation between renal expression and captopril effects; this gene also controls aganglionosis (see above, Monogenic traits) [408]
 Blood pressure: PAH Ddah1T
2, 251.63 Mb
The SD KO mutant shows no specific phenotype under control conditions, but exhibits exacerbated monocrotaline-induced PAH, lung fibrosis as well as right ventricule hypertrophy and dysfunction [409]
 Blood pressure: PAH Kcnk3T
6, 27.15 Mb
PAH KCNK3
2p23.3
The SD KO mutant shows predisposition to vasoconstriction of pulmonary arteries, strong alteration of right ventricular cardiomyocyte excitability and develops age-dependent PAH [410]
 Blood pressure: PAH Park7T
5, 167.98 Mb
Familial PD (recessive) PARK7 1p36.23 The KO mutant shows a worse degree of PAH than WT rats under hypoxia; the gene also controls Parkinson disease: see above, Monogenic traits [411]
 Blood pressure: PAH Slc39a12**,T
17, 81.46 Mb
Positional identification of the gene [WKY rats exposed to hypoxia show increased expression of Slc39a12 (ZIP12 protein)]; the KO WKY mutant shows attenuation of PAH [412]
 Blood pressure: PAH Sod3T
14, 61.07 Mb
In the SS KO mutant, the mutation favors PAH and subsequent RV hypertrophy under stress conditions [413]
 Blood pressure: PAH Trpc4T
2, 143.43 Mb
The F344 KO mutant shows reduced severity of pulmonary arterial occlusions and survival benefit in severe PAH (the gene is also involved in Pain, see below and Behavior, drug addiction: see above) [414]
 Blood pressure and QT-interval Rffl-lnc1***
10, 71.07 Mb
QT-interval 17q12 (RFFL region) Positional identification of the gene; the LEW allele contains a 19 bp deletion in the long non-coding RNA (5’UTR of Rffl), which increases blood pressure and shortens QT-interval relative to the SS rat (“cryptic allele”); the normal phenotypes were rescued by a specific targeted 19 bp insertion in the LEW allele [33]
 Body temperature Cckar*
14, 59.61 Mb
Gene deletion in the OLETF rat (no mapping of the trait): the gene seems also involved in diabetes and behavior; see above, Behavior, anxiety and below Diabetes type 2 [415, 416]
 Body weight (muscle mass) MstnT
9, 53.31 Mb
SS and SD KO mutants were studied; they show marked increases in muscle mass and lower fat content [417, 418]
 Body weight (liver mass) OgdhT
14, 86.41 Mb
Hypotonia, metabolic acidosis OGDH
7p13
The SD KO heterozygous mutant shows increased liver weight; high fat diet results in liver dysfunction (homozygous mutants are lethal) [419]
 Bone growth CftrT
4q21,
42.69 Mb
Cystic fibrosis CFTR
7q31.2
Young SD KO rats do not develop lung or pancreatic disease; however, they show a defect in linear bone growth and bone health that is attributed to IGF-1 deficiency (for Cystic fibrosis, see above, Monogenic traits) [420]
 Bone growth NppcT
9, 93.73 Mb
Short stature NPPC
2q37.1
The F344 KO mutant exhibits a deficit in endochondral bone growth and growth retardation [421]
 Bone structure and function BglapT
2, 87.74 Mb
The SD KO mutant shows increased trabecular thickness, density and volume, and increased bone strength [422]
 Brain development Bscl2ENU
1, 225.04 Mb
Congenital generalized lipodystrophy BSCL2
11q12.3
The KO mutant shows a slightly decreased brain weight and impairment of spatial working memory; see also above, Monogenic traits, Lipodystrophy, and Infertility [223]
 Brain injury Aqp4T
18, 6.77 Mb
Following subarachnoid hemorrhage, the KO mutant shows increased water content in the whole brain, which aggravates the neurological deficits through impairment of the glymphatic system. [423]
 Brain injury: acute cerebral infarction Uba6T
14, 23.51 Mb
The SD conditional KO mutant specifically lacks expression of the gene in the brain and shows aggravation of cerebral infarction, accompanied by increased level of apoptosis [424]
 Cancer, colon Rffl or Rffl-lnc1*
10, 70,16 Mb or 71.07 MB
Positional identification of the gene(s); higher expression of Rffl in S-LEW congenic rats, which also show higher expression of Mbd2 and higher susceptibility to colorectal carcinogenesis; see above, Blood pressure and QT-interval [425]
 Cancer, esophageal carcinoma Mir31T
5, 107.21 Mb
The SD KO mutant is resistant to zinc-deficiency associated esophageal carcinoma as a result of a strong reduction in an inflammatory process [426]
 Cancer, mammary (Mcs1a) Putative regulatory site**
2, ~ 6.50 Mb
Positional identification of the locus; cancer resistance is associated with increased expression of the nearby gene Nr2f1; the human homologous region (5q11-q34) is frequently deleted in breast cancers [427]
 Cancer, mammary (Mcs1b) Mier3**
2, 62.31 Mb
Breast cancer risk locus MAP3K1 or MIER3 5q11.2 Positional identification of the gene; higher expression in mammary glands of susceptible females [428]
Cancer, mammary (Mcs5a1) Fbxo10**
5, 60.59 Mb
Breast cancer risk locus FBXO10 (MCS5A1)
9p13
Positional identification of the gene; up-regulation in T cells is associated with susceptibility; causal SNVs are probably stress-responding regulatory sites [429, 430]
Cancer, mammary (Mcs5a2) Frmpd1**
5, 60.75 Mb
Breast cancer risk locus FRMPD1 (MCS5A2) 9p13 Positional identification of the gene; up-regulation in the spleen was associated with cancer resistance [430]
 Cancer, mammary (Mcs5c) Regulatory site**
5, ~ 81 Mb
Positional identification of the locus; Msc5c is located in a gene desert and regulates expression of the neighboring gene Pappa1 during a critical mammary developmental time period [431, 432]
 Cancer, mammary (Mcs30) Fry*
12, 7.68 Mb
Positional identification of the gene; several SNPs between F344 (susceptible) and COP (resistant); decreased expression of FRY in human cancers [433]
 Cancer, mammary gland development Cdkn1bT,
4, 168.69 Mb
Multiple endocrine neoplasia type 4 CDKN1B
12p13.1
In humans the frequency of a population of quiescent CDKN1B expressing cells was associated with breast cancer risk; the Cdkn1b KO ACI rat shows increased proliferation and pregnancy-associated changes in the mammary gland; Cdkn1b could impact mammary cancer risk; see also above, Monogenic traits, Cancer, multiple endocrine neoplasia and Obesity [83]
 Cardiac mass CfbT See below, Metabolic syndrome [434]
 Cardiac mass (Cm10) Endog**
3, 8.74 Mb
Positional identification of the gene, which is underexpressed in strains with increased cardiac mass; exonic mutation in SHR; Endog seems to be implicated in mitochondrial physiology [435]
Cardiac mass (LVM) Ogn**
17, 14.61 Mb
LVM OGN
9q22.31
Localization of a QTL and genome-wide gene expression studies associated upregulation ofOgn(due to sequence variation in theOgn3′ UTR) with elevated LVM; this finding was translated to humans [436]
 Cardiac mass, fibrosis Zbtb16**,T
8, 51.57 Mb
Positional identification of the gene in RI strains and in an SHR-PD congenic: deletion in the intron 2 of the PD allele, which is down-regulated and is protective; the heterozygous SHR KO mutant shows reduced cardiomyocyte hypertrophy and interstitial fibrosis (the homozygous KO is lethal) [406, 407]
 Cholesterol level and hepatic steatosis (Hpcl1) Srebf1***
10, 46.33 Mb
Cholesterol level and IFAP SREBF1
17p11.2
Positional identification of the gene; the SHR allele is associated with deficient expression of mRNA and protein; an SHR transgenic strain shows restoration of hepatic cholesterol level [437]
 Chronic kidney disease(CKD) Mir146b (5p)T
1, 266.09 Mb
CKD contributes to secondary cardiovascular impairment (cardiorenal syndrome type 4); in the surgical excision model of 5/6 nephrectomy, the KO SD female mutant shows sex-specific exacerbated renal hypertrophy and fibrosis with renal dysfunction yet lower blood pressure and less pronounced cardiac remodeling [438]
 Chronic kidney disease(CKD) Sod3ENU
14, 60.96 Mb
The SS mutant develops profound CKD characterized by focal necrosis and fibrosis, glomerulosclerosis, massive proteinaceous cast accumulation with tubular dilatation, interstitial fibrosis with hypertension and renal failure; see also below, Vascular function [439]
Diabetes, type 1: T1DM (Kdp1) Cblb***
11, 51.04 Mb
Diabetes, type 1 CBLB
3q13.11
Positional identification of the gene, mutated in the Komeda diabetes-prone rat; complementation with the WT gene significantly suppressed the phenotype of the KDP rats [440]
 Diabetes, type 1: T1DM (Iddm8) Dock8**
1, 242.93 Mb
Positional identification of the gene which harbors a missense mutation in the diabetic LEW.1AR1/Ztm-idmm rat [441]
 Diabetes, type 1: T1DM
Lymphopenia (Iddm2/lyp)
Gimap5**
4, 78.38 Mb
Systemic lupus erythematosus GIMAP5
7q36.1
Positional identification of the gene, mutated in the diabetes-prone BB rat; lymphopenia is essential for the development of the diabetic phenotype; in humans, GIMAP5 could play a role in the pathogenesis of systemic lupus erythematosus [442,443,444]
 Diabetes, type 1: T1DM (Iddm37) Ubd*, T
20, 1.87 Mb
Positional identification of Ubd, the promoter of which is polymorphic; high UBD expression is associated with virus-induced T1DM susceptibility (LEW.1WR1 rat for instance); an LEW.1WR1 KO rat shows reduced susceptibility, confirming the role of Ubd; the gene also controls cardiac ischemia (see above) [445]
 Diabetes, type 1: T1DM Ifnar1T
11, 31.64 Mb
T1DM Several genes acting downstream IFNAR1 Two LEW.1WR1 KO mutants were isolated; they exhibit, as expected, an impaired response to interferon I treatment; they are partially protected against virus-induced diabetes [446]
Diabetes, type 2: T2DM Adra2a**
1, 274.77 Mb
Increased T2DM risk ADRA2A
10q25.2
Positional identification of the gene, overexpressed in the diabetic Goto-Kakizaki rat, mediating adrenergic suppression of insulin secretion; association was then found betweenADRA2Aand increased T2DM risk in humans [447]
 Diabetes, type 2: T2DM Abcc8T
1, 102.11 Mb
T2DM and Hyperinsulinemic hypoglycemia and ABCC8
11p15.1
The SD KO mutant is glucose intolerant and shows enhanced insulin sensitivity; T2DM was induced in this mutant which was then treated with glimepiride (a sulfonylurea); the treatment decreased blood glucose levels, suggesting an extra-pancreatic, direct effect on insulin-sensitive tissues [448, 449]
 Diabetes, type 2: T2DM (Odb2) Cckar**
14, 59.61 Mb
Positional identification of the gene, deleted in the OLETF rat; mapping studies suggest an interaction with an X-linked QTL; the gene might also control pancreatic duct hyperplasia; see also above, Body temperature and Behavior, anxiety [450, 451]
Diabetes: T2DM (Insulin resistance and hyperlipidemia) Cd36***
4, 14.15 Mb
T2DM: Insulin resistance, dyslipidemia CD36
7q21.11
Positional identification of the gene, combined with genome-wide gene expression studies;Cd36is deleted in the SHR strain; transgenic expression ofCd36in SHR ameliorates insulin resistance and lowers serum fatty acids; association of humanCD36with T2DM; the gene also controls blood pressure: see above [30,31,32]
Diabetes, type 2: T2DM (Nidd/gk1) Inppl1**
1q33
166.90 Mb
T2DM INPPL1
11q13.4
Positional identification of the gene, mutated in the Goto-Kakizaki diabetic rat (and the insulin-resistant SHR); mutations were then found in human diabetic patients [452]
 Diabetes, type 2: T2DM (diet-induced) Ndufa4*
4, 38.23 Mb
Positional identification of the gene, which shows a 61 bp deletion, unique to the Cohen diabetic rat; this mutation adversely affects mitochondrial function and promotes diet-induced diabetes [453]
 Diabetes, type 2: T2DM (fat mass and insulin resistance) PpargENU
4, 147.27 Mb
Lipodystrophy and insulin resistance PPARG
3p25.2
The heterozygous F344 missense mutant shows reduced fat mass with adipocyte hypertrophy and insulin resistance (the homozygous mutant is lethal) [454]
 Diabetes, type 2: T2DM (Dmo1) Prlhr**
1, 289.10 Mb
Blood pressure PRLHR
10q26.13
Positional identification of the gene; point mutation at translation initiation codon in the OLETF rat; the mutation causes hyperphagia [455]
 Diabetes, type 2: T2DM Tbc1d4T
15, 85.93 Mb
Increased T2DM risk TBC1D4
13q22.2
The Wistar KO mutant shows glucose intolerance and insulin resistance [456]
 Diabetes, type 2: T2DM (beta cell lipotoxicity) Tlr4T
5, 82.59 Mb
The SD KO mutant shows delayed damage induced by high-fat diet, improved beta-cell function, decreased pancreatic inflammatory infiltration and apoptosis; see also below, Inflammation [457]
Diabetes, type 2: T2DM Tpcn2***
1, 218.42 Mb
Fasting insulin TPCN2
11q13.3
QTL was detected in a HS; differential expression ofTpcn2; nonsynonymous coding variant as well as other SNPs were associated with fasting glucose;TPCN2was associated with fasting insulin in humans [458]
 Diabetes, type 2: T2DM (Diabetic kidney disease) Trpc6T
8, 6.81 Mb
Familial focal segmental glomerulosclerosis TRPC6
11q22.1
The results indicate that TRPC6 channel inhibition (in the SS rat background) has partial renoprotective effects in diabetic rats [459]
 Encephalo-myelitis (EAE) Cd8aENU
4, 163.99 Mb
The KO Lewis mutant is protected from EAE [460]
 EAE Clec4d**
4, 156.25 Mb, and
Clec4e**
4, 156.27 Mb
Multiple sclerosis Positional identification of the genes; rat strains expressing lower levels of Clec4d and Clec4e on myeloid cells exhibit a drastic reduction in EAE incidence; the CLEC4D/CLEC4E signaling pathway is upregulated in peripheral blood mononuclear cells from MS patients [461]
 EAE Dlk1**
6, 142.74 Mb
IDDM (depending of parental origin) DLK1
14q32
Parent-of-origin dependent QTL; the paternal PVG risk allele predisposes to low Dlk1 expression [462]
 EAE: Eae1 Btnl2*
20p12, 6.22 MB and
RT1-Db1*
20p12,
6.17 Mb
Multiple sclerosis HLA-DRB1
6p21.3
Positional identification: the two genes in the MHC class II locus were identified in a HS and are the best candidate variants, amongst 3 candidate genes [350]
EAE:Eae30 Rgma*
1, 134.70 Mb
Multiple sclerosis RGMA
15q26.1
Positional identification of the rat gene but polymorphisms ofRgmawere not sought; it is thus a suggestive causal gene; however this result led to the discovery that a SNP inRGMAis associated with multiple sclerosis in humans [463]
EAE:Eae4 Vav1**
9q12, 8.6 Mb
Multiple sclerosis VAV1
19p13.2
Positional identification of the gene: one SNP in rat exon 1 correlates with EAE susceptibility and high TNF; in humans, association found betweenVAV1haplotype (high expression) and multiple sclerosis; the gene also regulates arthritis (see above) [341, 464]
EAE:Eae31; Pia32 Il21r*
1, 197.00 Mb
Multiple sclerosis IL21R
16p12.1
Positional identification of the rat gene but polymorphisms ofIl21rwere not sought; however this result led to the discovery that SNP’s inIL21Rare associated with multiple sclerosis in humans [463]
EAE:Eae29; Pia8 Il22ra2**
1, 15.09 Mb
Multiple sclerosis IL22RA2
6q23.3
The susceptible strain DA carries a unique variant of the gene, which is differently expressed; a SNP inIL22RA2was associated with multiple sclerosis in humans [330, 465]
 Experimental autoimmune neuritis: Ean6 Ncf1*
12, 25.50 Mb
Guillain-Barré syndrome Positional identification of the gene, a suggestive causal gene: no polymorphism between strains was sought but functional studies support the role of Ncf1 (the gene also controls EAE and PIA: see above) [466]
 Epilepsy (idiopathic, generalized; GAERS) Cacna1h**
10, 14.73 Mb
Absence epilepsy CACNA1H
16p13.3
Direct sequencing of the gene showed a mutation in the Genetic Absence Epilepsy Rats from Strasbourg (and not in non-epileptic strains); in an F2 cross, the phenotype segregates with the mutation [467]
 Epilepsy, tremor Hcn1**, T
2, 50.10 Mb
Infantile epileptic encephalopathy HCN1
5p12
Positional identification of the gene; a typical example of epistasis: rats (TRM/Kyo) possessing a large deletion (tm) on chromosome 10 (240 Kb; 13 genes) exhibit tremor if they also possess the allele Hcn1A354V; when this allele is replaced by Hcn1V35A tremor is absent (TRMR rats); subsequently, an F344 KO mutant was generated and showed susceptibility to induced seizure [468, 469]
 Glomerulonephritis (Crgn8) Cp**
2, 104.74 Mb
Positional identification of the gene in combination with genome-wide eQTL mapping and functional tests; ceruloplasmin is overexpressed in WKY macrophages [470]
Glomerulonephritis(Crgn1) Fcgr3-rs**
13, 89.38 Mb
Glomerulonephritis in systemic lupus
erythematosus
FCGR3B
1q23.3
Positional identification of the loss of anFcgr3paralog as a determinant of glomerulonephritis in WKY rats; expressing the gene in primary WKY macrophages results in low levels of phagocytosis; in humans, association found between low copy number ofFCGR3Band lupus nephritis [471, 472]
 Glomerulonephritis (Crgn2) Jund**
16, 20.48 Mb
Localization of a QTL and genome-wide gene expression studies associated upregulation of Jund (due to a SNP in the promoter region) with glomerulonephritis; Jund KO in primary macrophages led to reduced macrophage activity [473]
 Glomerulonephritis Kcnn4**
1, 81.22 Mb
Genome-wide eQTL mapping in macrophages from a segregating population led to the identification of Kcnn4 as a key regulator of macrophage multinucleation and inflammatory diseases; Kcnn4 is trans-regulated by Trem2 [474]
 Glucose homeostasis Tbc1d1T
14, 45.60 Mb
CAKUT TBC1D1
4p14
The SD KO mutant shows impaired contraction-induced sarcolemmal glucose transporter 4 redistribution, impaired glucose-tolerance and reduced pancreatic beta-cell mass [475,476,477]
 Heart failure Ephx2**
15, 42.76 Mb
Localization of a QTL and genome-wide gene expression studies associated upregulation of Ephx2 (due to a sequence variation in the promoter region) with heart failure susceptibility [478]
 Herpes simplex encephalitis susceptibility: Hse1 Calcr*
4q13,
28.53 Mb
Differences in expression level of Calcr mRNA and in protein localization between the susceptible (DA) and resistant (PVG) strains [479]
 Hippocampus function Trpm4T
1, 101.29 Mb
The SD KO mutant shows a distinct deficit in spatial working and spatial memory as well as changes in various target regions of the right dorsal hippocampus upon stimulation of Schaffer collaterals [480, 481]
Inflammation: Irf7-driven inflammatory network Gpr183**
15q15,
108.36 Mb
IDDM GPR183
13q32
Gene expression analyses and QTL mapping done in the rat; the results were translated to humans, identifyingGPR183(=EBI2)as a type 1 diabetes susceptibility gene [482]
 Inflammation: TNF induction Tlr4T
5, 86.69 Mb
The Wistar KO rat shows markedly reduced TNF induction upon liposaccharide challenge; see also above, Diabetes, type 2 [483]
 Insulin resistance Pparg**    See above, Diabetes type2, Fat mass  
 Macrophage development Csf1rT
18, 56.41 Mb
ALSP CSF1R
5q32
The DA KO mutant shows multiple abnormalities: loss of macrophages in several organs, osteopetrosis, infertility, lack of tooth eruption, loss of visceral fat, absence of microglia; see above, Mongenetic traits, toothless for mutation in Csf1 [60]
 Macrophage function Cyp2j4T
5, 119.55 Mb
The WKY KO mutant macrophages show a profibrotic transcriptome; the macrophage epoxygenase could thus play a role in fibrotic disorders with inflammatory component; see also below, Metabolic syndrome [484]
 Metabolic syndrome (Niddm30) Camk2n1T
5, 156.88 Mb
Elevated risk of T2DM and coronary heart disease CAMK2N1
1p36.12
The gene was a solid candidate gene for metabolic syndrome (blood pressure, diabetes, left ventricule weight); the SHR KO rat shows reduced cardiorenal Camk2 activity, lower blood pressure, lower left ventricular mass, decreased visceral fat mass and increased insulin sensitivity [485]
Metabolic syndrome CfbT
20p12,
4.54 Mb
NIDDM and components of metabolic syndrome CFB
6p21.33
The SHR KO rat shows improved glucose tolerance and adipose distribution, lower blood pressure, and reduced left ventricular mass; several human SNPs inCFBwere associated with cardiometabolic traits [434]
 Metabolic syndrome Cyp2j4T
5, 119.55 Mb
The WKY KO mutant shows adipocyte hypertrophy and weight gain; under “cafetaria diet”, it shows hepatic lipid accumulation, dysregulated gluconeogenesis and increased triglyceride levels; see also above, Macrophage function [486]
 Metabolic syndrome Folh1**
1, 150.32 Mb
Positional identification of the gene; the SHR allele shows 2 missense mutations; an SHR congenic line harboring the BN Folh1 allele shows decreased glucose and insulin concentrations [487]
 Metabolic syndrome Folr1***
1, 166.93 Mb
Positional identification of the gene, the promoter of which is mutated in the SHR; transgenic rescue experiments ameliorate most of the metabolic disturbances, probably linked to folate deficiency and hypercysteinemia [488]
 Metabolic syndrome Gja8**2, 199.05 Mb The Gja8 mutation present in the SHR-Dca strain causes dominant cataract (see above, Monogenic traits); in the heterozygous form this mutation results in increased concentration of triacyl-glycerols, decrease of cholesterol and elevation of inflammatory cytokines [489]
 Metabolic syndrome Mt-Nd2, Mt-Nd4, Mt-Nd5 The conplastic rat SHR-mtLEW only differs from SHR in the sequence of these 3 mitochondrial genes and exhibits increased serum fatty acid levels and resistance to insulin stimulated incorporation of glucose into adipose tissue lipids [490]
 Metabolic syndrome Wars2***
2q34,
201.17 Mb
Cardio-metabolic phenotypes WARS2
1p12
Positional identification of the gene; the SHR allele is mutated (and causes reduced angiogenesis – see above); transgenic SHR-Wars2 rats exhibit increased glucose oxidation and incorporation into brown adipose tissue, as well as lower adiposity [491]
 Metabolic syndrome Zbtb16T
8, 51.57 Mb
The heterozygous SHR KO rat exhibits lower serum and triglycerides and cholesterol as well as increased sensitivity to adipose and muscle tissue to insulin action [407]
 Metabolic syndrome: obesity Aqp11**
1, 162.70 Mb
Positional identification of the gene in combination with expression QTL mapping; the LH rat allele is mutated in the 3′ UTR and the 5′ upstream region; downregulation of Aqp11 is associated with obesity in the LH rat; aquaporins are now considered to be involved in adipose tissue homeostasis [492]
 Metabolism Apoa4T
8q23,
50.54 Mb
The SD KO mutant shows improved glucose tolerance and altered expression of genes expressed in the liver, with enhanced glycolysis, attenuated gluconeogenesis and elevated de novo lipogenesis [493]
 Metabolism Esr1T
1q12,
41.19 Mb
The male SD KO liver shows altered expression of genes involved in carbohydrate and lipid metabolism; see also above, Monogenic traits, Infertility [494]
 Metabolism PmchENU
7, 28.65 Mb
The Wistar KO mutant is lean, hypophagic, osteoporotic and has a low adipose mass due to a lower adipocyte cell size [495, 496]
 Metabolism (steroid synthesis) TspoT
7, 124.46 Mb
Anxiety-related disorders TSPO The SD KO mutant displays impaired ACTH-induced steroid production and reduced circulating testosterone levels; in humans a rare TSPO allele is associated with a reduced plasma cortisol rate of formation [497]
 Neuromyelitis optica spectrum disorders Cd59T
3, 94.01 Mb
The SD KO mutant shows no overt phenotype, except for mild hemolysis; however upon intracerebral administration of autoantibodies against astrocyte aquaporin 4, it shows marked neuromyelitis optica pathology including inflammation and demyelination [498]
 Non-alcoholic fatty liver disease PtenT
1, 251.42 Mb
This study reports the somatic inactivation of Pten in the liver (by injection of an inactivating plsmid); the treated SD rats showed increased body weight and triglyceride level, with increased lipid accumulation in the liver [499]
 Oxidative stress- mediated cell death Keap1T
8, 22.25 Mb
Grafting of mesenchymal stem cells is hampered by oxidative stress-mediated cell death; Keap1 was knocked- down in adipose-derived mesenchymal stem cells leading to the activation of NFE2L2 and lower oxidative stress [500]
 Pain Scn9aT e
3, 52.58 Mb
The SD KO e rat does not exhibit nociceptive pain responses in hot plate nor neuropathic pain responses following spinal nerve ligation; inhibition of SCN9A in humans may thus reduce pain in neuropathic conditions [501]
 Pain Trpv1T
10, 59.80 Mb
Neuroimaging experiments of SD KO and WT rats showed that capsaicin-induced pain activates neuronal circuitries involved in pain but also in emotion and memory in a TRPV1-dependent manner; this channel was shown to be dispensable for hypernatremia-induced vasopressin secretion [502, 503]
 Pain (visceral nociception) Trpc4T
2, 143.43 Mb
The F344 KO rat is tolerant to noxious chemical stimuli applied to the colon (the gene is also involved in Blood pressure control -PAH- and Behavior, drug addiction: see above) [504]
 Pain processing Ano3T
3, 108.44 Mb
The F344 KO rat shows increased neuronal activity and increased thermal and mechanical sensitivity [505]
 Proteinuria (Pur1) Actr3**13, 46.81 Mb Positional identification of the gene: sole gene mutated in the Pur1 interval of the BUF/Mna rat (a model of glomerulosclerosis) [506]
 Proteinuria AgtrapT
5, 168.55 Mb
Renal function AGTRAP-PLOD1 locus; 1p36 The SS KO rat shows decreased urinary protein excretion; the human locus had been identified in GWAS [39]
 Proteinuria Clcn6T
5, 168.47 Mb
Renal function AGTRAP-PLOD1 locus; 1p36 The SS KO rat shows decreased urinary protein excretion; the human locus had been identified in GWAS [39]
 Proteinuria MthfrT
5, 168.50 Mb
Renal function AGTRAP-PLOD1 locus; 1p36 The SS KO rat shows increased urinary protein excretion; the human locus had been identified in GWAS and MTHFR could be linked to blood pressure and renal phenotype [39]
 Proteinuria Plod1T
5, 168.38 Mb
Renal function AGTRAP-PLOD1 locus; 1p36 The SS KO rat shows increased urinary protein excretion; the human locus had been identified in GWAS [39]
 Proteinuria (Rf2) Rab38***,T
1, 152.07 Mb
Natural KO in FHH; transgenesis in FHH and targeted KO in a FHH.BN congenic demonstrated the role of Rab38 in protein excretion [507]
 Proteinuria and kidney damage Add3***
1q55,
273.85 Mb
Positional identification and sequencing of the FHH gene revealed a deleterious mutation; knockout and transgenesis experiments confirmed the causal role of the mutation [508, 509]
 Proteinuria and kidney damage (Rf4) Shroom3**
14, 16.62 Mb
Renal function SHROOM3
(GWAS)
4q21.1
Congenic mapping and sequence analysis in rats suggested that Shroom3 was a strong positional candidate gene; variants disrupting the actin-binding domain of SHROOM3 may cause podocyte effacement and impairment of the glomerular filtration barrier in zebrafish [510]
 Proteinuria and kidney damage TgfbT
1, 83.74 Mb
Heterozygous KO of Tgfb protects the SS rat against high salt-induced renal injury [511]
 Proteinuria and kidney damage Tmem63c*
6, 111.04 Mb
Positional identification of the gene, which shows differential glomerular expression; the susceptible strain (MWF) also shows a nephron deficit; patients with focal segmental glomerulosclerosis exhibit loss of glomerular TMEM63C expression [512]
Proteinuria and kidney damage (Pur7?) Arhgef11**
2, 206.39 Mb
Glomerular filtration rate 1q21 Positional identification of the gene; allelic variants are differentially expressed in SS, SHR and congenic rats [513]
Proteinuria and kidney disease (Rf1) Sorcs1**,T
1, 277.40 Mb
Kidney disease SORCS1
10q23-q25
TheRf1interval was narrowed down to a single gene,Sorcs1, which only shows polymorphisms in non-coding regions;Sorcs1KO in the consomic FHH-1BNcauses increased proteinuria and impairment of albumin transport; in humans, association was found betweenSORCS1and kidney disease [514]
 QT-interval Rffl-lnc1***    See above, Blood pressure and QT-interval [33]
 Renal injury Nr4a1T
7, 142.90 Mb
The FHH KO rat shows early onset of kidney injury and progressive decline in kidney function resulting from macrophage-mediated enhanced inflammatory processes; the gene is also involved in dyskinesia (see above, Monogenic traits, Parkinson disease model) and in Behavior, Stress response (see above) [515]
 Renal injury Serpinc1T
13, 78.81 Mb
Patients with low SERPINC1 activities present a higher risk of developing AKI after cardiac surgery; the heterozygous congenic SS.BN KO rat shows increased renal injury after renal ischemia/reperfusion [516]
 Renal injury Stim1***
1, 167.37 Mb
Autoimmunity STIM1
11p15.4
Genome sequencing revealed a deletion affecting the Stim1 gene is the SHR-A3 which develops renal injury; a congenic line with a functional Stim1 gene shows an improved lymphocyte function and a strong reduction in renal injury and glomerular immunoglobulin deposition; this pleiotropic genes also controls Diabetes insipidus (see above, Monogenic traits), Behavior (stress response, see above, Polygenic traits) and Stroke (see below) [517]
 Rheumatoid factor production Igl**
11, 83.93 Mb
Analysis of congenic and advanced intercrossed rats showed that the Igl locus controls rheumatoid factor production and allergic bronchitis [518]
 Spermatogenesis Tp53T
10q24,
56.19 Mb
Li-Fraumeni syndrome TP53
17p13.1
The SD KO mutant shows testicular atrophy, spontaneous spermatocyte death and germ cell depletion; Tp53 also controls Cancer development: see above, Monogenic traits [519]
 Stroke Igh*
6, ~ 138 Mb
Congenic substitution of the SHRSP Igh locus with the corresponding haplotype from SHR (stroke-resistant) reduced cerebrovascular disease, as well as the serum levels of autoantibodies to key cerebrovascular stress proteins [520]
Stroke(Str1) Ndufc2*,T
1, 162.37 Mb
Stroke NDUFC211q14.1 Positional identification of the gene and differential expression study:Ndufc2is down-regulated in SHRSP (no sequence difference between SHRSP and SHRSR); the heterozygous SHRSR KO rat shows stroke occurrence and renal abnormalities, similarly to the SHRSP rat; in humans, association was found betweenNDUFC2and stroke [35, 36]
Stroke (Str2) Nppa**
5, 165.81 Mb
Stroke NPPA
1p36.21
Positional identification of the gene; altered sequence and expression ofNppain the SHRSP rat; in humans, association was found betweenNPPAand stroke [521, 522]
 Stroke Stim1***
1, 167.37 Mb
Autoimmunity STIM1
11p15.4
Genome sequencing revealed a deletion affecting the Stim1 gene is a stroke-prone subline (SHR-A3); a congenic line with a functional Stim1 gene shows a strong reduction in stroke susceptibility; Stim1 deficiency results in the generation of auto-antibodies; this pleiotropic genes also controls Diabetes insipidus (see above, Monogenic traits), Behavior (stress response) and Renal injury (see above, Polygenic traits) [523]
 Stroke: neuronal apoptosis Klf5T
15, 83.70 Mb
The SD KO rat with induced ischemic stroke shows reduction of infarct size and of apoptotic neuronal loss; KLF5 stimulates stroke-induced neuronal apoptosis [524]
 Stroke: neuronal apoptosis Mir195T
10, 56.84 Mb
The SD KO rat with induced ischemic stroke shows increased infarct size and apoptotic neuronal loss; Mir195 down-regulates Klf5 expression [524]
 T-cell differentiation Pon1T
4, 30.25 Mb
The SD KO rat shows a decrease in CD4+, CD8+ and double-positive T-cells; PON1 prevents excessive apoptosis by inhibiting activation of the p38 signaling pathway [525]
 T-cell differentiation Tap2**
20p12,
3.99 Mb
+ RT1-A**
20p12,? Mb
Positional identification of Tap2 and RT1-A, which interact with one another and control CD4:CD8 ratio and MHC class expression [526]
 Toxicity AhrT
6, 54.97 Mb
The SD KO mutant shows renal pathology and lack of responses to dioxin exposure (Ahr KO results in distinct phenotypes in mouse and rat) [527]
 Toxicity Nr1i2T
2, 65.02 Mb
An F344 KO mutant does not show the increase in NADPH-cytochrome P450 oxidoreductase protein and activity upon dexamethasone treatment; on the other hand, unlike wild-type rats, the SD KO rat fed diet containing pregnenolone-16alpha-carbonitrile (a non-genotoxic carcinogen) does not show increased thyroid gland weight [528, 529]
 Toxicity (liver) Nr1i3T
13, 89.59 Mb
Unlike wild-type rats, the SD KO rat fed diet containing sodium phenobarbital (a non-genotoxic carcinogen) does not show increased liver weight, hepatocyte replicative DNA synthesis and induction of cytochrome P450 enzymes [529]
 Vascular function Mc4rENU
18, 62.61 Mb
Obesity MC4R18q22 The MSH6 KO rat is obese (see above) and shows bradycardia and increased sympathetic tone to the vasculature [530]
 Vascular function Nfe2l2T
3, 623.50 Mb
The SD KO rat shows abnormalities in endothelium-dependent vasodilation and in microvessel density (Nfe2l2 also controls aflatoxin B1 toxicity: see above) [531]
 Vascular function (vasodilation) Sod3ENU
14, 60.96 Mb
Missense mutation in the SS rat with deleterious effects on aortic vascular reactivity, but protective effects in mesenteric arteries; see also above, Chronic kidney disease [532]
 Vascular tone and nephropathy Shc1T
2, 188.75 Mb
The SS rat overexpresses Shc1, a feature linked to hypertension-induced increased renal damage; Shc1 KO restores renal microvascular responses and mitigates glomerular damage in the SS rat [533]
  1. a In forward genetic studies, the role of the causative genes is considered proven when complementation, mutation recovery, gene disruption or transgenesis was performed successfully (***); when these tests are lacking, the role of the gene can be either solid (**) (polymorphisms analysed in several contrasting strains, genetic linkage in a cross, or translation to genetic association in the human), or suggestive only (*) (for instance, polymorphism analysed in 2 contrasting strains only). Genes inactivated by ENU-driven target-selected mutagenesis are labeleled as ENU. Targeted mutations (in general, KO rats) are labelled as T
  2. b The human gene is indicated only when it has been implicated in the trait or diseases analysed in the rat
  3. c The gene positions are based on the data available at the NCBI (www.ncbi.nlm.nih.gov/), except those of the Lta-Ncr3 region, derived from [338]; in the case of the rat, the cytogenetic position is indicated only when it was determined by in situ hybridization
  4. d The genomic scan of replicated high- and low-alcohol-drinking lines revealed signature of selection (excessive differentiation in the genomic architecture between lines) in 930 genes [320]; in the above table, only those genes residing in previously identified QTLs are quoted.
  5. e This mutant is in fact a knock-in mutant carrying a human insertion that, unexpectedly, was shown to be spliced out upon transcription, resulting in the generation of a premature stop codon and thus in a loss-of-function allele (except in the olfactory bulb)
  6. Abbreviations used in the table:
  7. 1) Genes: Abcb1a ATP-binding cassette, sub-family B (MDR/TAP), member 1A (=Mdr1a, Multidrug resistance 1a/P-glycoprotein), Abcc2 ATP-binding cassette, sub-family C (CFTR/MRP), member 2 (=Moat = Mrp2), Abcc6 ATP binding cassette subfamily C member 6, Abcc8 ATP binding cassette subfamily C member 8 (=Sur1, Sulfonylurea receptor 1), Abcg2 ATP-binding cassette, sub-family G (WHITE), member 2 (Junior blood group) (=Bcrp, Breast cancer resistance protein), Abcg5 ATP-binding cassette, sub-family G (WHITE), member 5, ABCG8 ATP-binding cassette, sub-family G (WHITE), member 8, Actr3 ARP3 actin-related protein 3 homolog (yeast), Adamts16 Disintegrin and metallopeptidase with thrombospondin type 1 motif, 16, Adcyap1r1 Adenylate cyclase activating polypeptide receptor type 1, Add1 Adducing 1 (alpha), Add3 Adducing 3 (gamma), Agtr1a Angiotensin II receptor, type 1a, Adgrl3 Adhesion G protein-coupled receptor L3 (=Lphn3), Adra2a Adrenoceptor alpha 2A, Ahr Aryl hydrocarbon receptor, Angptl8 Angiopoietin-like 8, Anks6 Ankyrin repeat and sterile alpha motif domain containing 6 (= Pkdr1, SamCystin), Ano3 Anoctamin 3, calcium activated chloride channel (=Tmem16c), Apc Adenomatous polyposis coli, Aplec Antigen-presenting lectin-like receptor gene complex (=Dcir3), Apoa4 Apolipoprotein A4, Apoe Apolipoprotein E, Aqp4 Aquaporin 4, Aqp11 Aquaporin 11, Ar Androgen receptor, Arntl Aryl hydrocarbon receptor nuclear translocator-like (=Bmal1), Ar Androgen receptor, Arhgef11 Rho guanine nucleotide exchange factor (GEF) 11, Arsb Arylsulfatase B, Asip Agouti signaling protein, Aspa Aspartoacylase, Atm Ataxia-telangiectasia mutated serine/threonine kinase, Atp7b ATPase, Cu++ transporting, beta polypeptide, Atrn Attractin, Avp Arginin vasopressin, Bace1 Beta-secretase 1, Bckdk Branched chain ketoacid dehydrogenase kinase, Bdnf Brain-derived neurotrophic factor, Bglap Bone gamma-carboxyglutamate protein (=osteocalcin), Brca2 BRCA2, DNA repair associated, Bscl2 BSCL2 lipid droplet biogenesis associated, seipin, CIIta Class II, major histocompatibility complex, transactivator (=Mhc2ta), C3 Complement C3, Cacna1a Calcium channel voltage-dependent subunit alpha 1A, Cacna1c Calcium voltage-gated channel subunit alpha1 C, Cacna1f Calcium voltage-gated channel subunit alpha1 F, Cacna1h Calcium voltage-gated channel subunit alpha1 H, Calcr Calcitonin receptor, Camk2 Calcium/calmodulin-dependent protein kinase II, Camk2n1 Calcium/calmodulin-dependent protein kinase II inhibitor 1, Cav3 Caveolin 3, Cblb Cbl proto-oncogene B, Ccdc39 Coiled-coil containing domain 39, Ccdc85c Coiled-coil containing domain 85C, Cckar Cholecystokinin A receptor, Cd8a Cd8A molecule, Cd36 CD36 molecule, fatty acid translocase, Cd59 Cd59 molecule, Cd247 CD247 molecule (CD3 zeta chain), Cdh13 Cadherin 13, Cdkn1b Cyclin dependent kinase inhibitor 1B, Cfb complement factor B, Cftr Cystic fibrosis transmembrane conductance regulator, Chrm3 Cholinergic receptor, muscarinic 3, Cit Citron rho-interacting serine/threonine kinase, CLEC4A C-type lectin domain family 4, member A (=DCIR), Clec4b C-type lectin domain family 4, member B, Clec4d C-type lectin domain family 4 member D (=Mcl), Clec4e C-type lectin domain family 4 member E (=Mincle), Cntnap2 Contactin associated protein like 2, Cntrob Centrobin, centrosomal BRCA2 interacting protein, Cp Ceruloplasmin, Cplx1 Complexin 1, Crb1 Crumbs cell polarity complex component 1, Crebbp CREB binding protein (=Cbp), Crhr2 Corticotropin releasing hormone receptor 2, Cryba1 Crystallin beta A1, Crygd Crystallin gamma D, Csf1 Colony stimulating factor 1, Csf1r Colony stimulating factor 1 receptor, Ctnnd2 Catenin (cadherin-associated protein), delta 2, Ctns Cystinosin, lysosomal cystin transporter, Cyba Cytochrome b-245 alpha chain, Cyp2c11 Cytochrome P450, family 2, subfamily c, polypeptide 11, Cyp2e1 Cytochrome P450, family 2, subfamily e, polypeptide 1, Cyp2j4 Cytochrome P450, family 2, subfamily j, polypeptide 4 (human CYP2J2 ortholog, epoxygenase), Cyp3a1/2 Cytpchrome P450, family 3, subfamily a, polypeptide 1/2, Cyp4f18 Cytochrome P450, family 4, subfamily f, polypeptide 18, Cyp11b1 Cytochrome P450, family 11, subfamily b, polypeptide 1, Cyp17a1 Cytochrome P450 family 17, subfamily a, polypeptide 1, Cyp27b1 Cytochrome P450 family 27 subfamily B member 1, Dao D-amino-acid oxidase, Ddah1 Dimethylarginine dimethylaminohydrolase 1, Defb23/26/42 Defensin beta 23/26/42, Depdc5 DEP domain containing 5, Dhh Desert hedgehog, Dmd Dystrophin, Disc1 Disc1 scaffold protein, Dnd1 DND microRNA-mediated repression inhibitor 1, Dnmt1 DNA methyltransferase 1, Dock8 Dedicator of cytokinesis 8, Dopey1 Dopey family member 1, Dpp4 Dipeptidyl peptidase 4, Drd1 Dopamine receptor D1, Dsg4 Desmoglein 4, Dusp5 Dual specificity phosphatase 5, Endog endonuclease G, Ephx2 Epoxide hydrolase, Ercc6 ERCC excision repair 6, chromatin remodelling factor (=Csb: Cockayne syndrome B), Esr1 Estrogen receptor 1, Esr2 Estrogen receptor 2, Edaradd EDAR-associated death domain, Ednrb Endothelin receptor type B, F8 Coagulation factor F8, Fah Fumarylacetoacetate hydrolase, Fam129c Family with sequence similarity 129, member C, Fbxo10 F-box protein 10, Fcgr1a Fc fragment of IgG receptor Ia, Fcgr2a Fc fragment of IgG receptor IIa, FCGR3B Fc fragment of IgG receptor IIIb, Fcgr3-rs Fc fragment of IgG receptor III related sequence, Fdft1 Farnesyl diphosphate farnesyltransferase1, Fh fumarate hydratase, Fkbp5 FKBP prolyl isomerase 5, Flcn Folliculin (=Bhd, Birt-Hogg-Dube syndrome homolog), Fmr1 Fragile X mental retardation 1, Folh1 Folate hydrolase 1, Folr1 Folate receptor 1, Foxn1 Forkhead box N1, Frem2 FRAS1 related extracellular matrix protein 2, Frmpd1 FERM and PDZ domain containing 1, Fry Furry homolog (Drosophila), Gdnf Glial cell derived neurotrophic factor, Gh growth hormone, Ghsr Growth hormone secretagogue (ghrelin) receptor, Gimap5 GTPase, IMAP family member 5 (=Ian4/5), Git2 GIT ArfGAP 2, Gja3 Gap junction protein, alpha 3, Gja8 Gap junction protein, alpha 8 (=Cox50), Gla Galactosidase alpha, Gnal G protein subunit alpha L, Golgb1 Golgin B1, Gper1 G protein-coupled estrogen receptor 1, Gpr183 G protein-coupled receptor 183 (=Ebi2), Grin2a Glutamate ionotropic receptor NMDA type subunit 2A, Grm2 Glutamate metabotropic receptor 2 (=mGlur2), Hcn1 Hyperpolarization activated cyclic nucleotide gated potassium channel 1, Hip1 Huntington-interacting protein 1, Hmx1 H6 family homeobox 1, Hr Hair growth associated, Hsd11b2 Hydroxysteroid 11-beta dehydrogenase 2, Htr7 5-hydroxytryptamine (serotonin) receptor 7, adenylate cyclase-coupled, Igh Immunoglobulin heavy chain locus, Igl Immunoglobulin lambda chain complex, Il1rl2 Interleukin 1 receptor like 2 (=Il36r), Il2rg Interleukin 2 receptor, gamma, Il21r Interleukin 21 receptor, Il22ra2 Interleukin 22 receptor, alpha 2, Inppl1 Inositol polyphosphate phosphatase like 1, Isca1 Iron-sulfur complex assembly 1, Jund JunD proto-oncogene, AP-1 transcription factor subunit, Kcna1 Potassium voltage-gated channel, shaker-related subfamily, member 1, Kng2 Kininogen 2, Kcnj1 Potassium voltage-gated channel subfamily J member 1 (=Romk), Kcnj10 Potassium voltage-gated channel subfamily J member 10 (=Kir4.1), Kcnj16 Potassium voltage-gated channel subfamily J member 16, Kncq1 Potassium voltage-gated channel, KQT-like subfamily, member 1, Kcnk3 Potassium two pore domain channel subfamily K member 3, Kcnn2 Potassium calcium-activated channel subfamily N member 2, Kcnn4 Potassium calcium-activated channel subfamily N member 4, Keap1 Kelch like ECH associated protein 1, Kiss1 KISS-1 metastasis-suppressor (kisspeptin), Kit v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog, Klf5 Kruppel-like factor 5, Krt@ Cytokeratin gene locus (type II), Krt71 Keratin 71, L1cam L1 cell adhesion molecule, Lamp2 Lysosomal associated membrane protein 2, Ldlr Low density lipoprotein receptor, Lep Leptin, Lepr Leptin receptor, Lgi1 Leucine rich glioma inactivated 1, Lipa Lipase A, lysosomal acid, cholesterol esterase, Lmx1a LIM homeobox transcription factor 1, alpha, Lpar1 Lysophosphatidic acid receptor 1, Lpin1 Lipin 1 (phosphatidate phosphatase), Lrp5 LDL receptor related protein 5, Lrrk2 Leucine-rich repeat kinase 2, Lss Lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase), Lta Lymphotoxin alpha, Ltb Lymphotoxin beta, Lst1 Leukocyte-specific transcript 1, Lyst Lysosomal trafficking regulator, Mas1 MAS1 proto-oncogen, G-protein-coupled recptor, Mbd2 Methyl CpG binding domain binding protein 2, Mbp Myelin basic protein, Mc4r Melanocortin 4 receptor, Mecp2 Methyl-CpG binding protein 2, Mertk MER proto-oncogene, tyrosine kinase, Mip Major intrinsic protein of lens fiber, Mir31 Micro RNA 31, Mir146b (5p) Micro RNA 146b, Mir195 Micro RNA 195, Mkx Mohawk homeobox, Mrs2 MRS2 magnesium transporter, Msh6 MutS homolog 6, Mstn Myostatin, Mt-Nd2, Mt-Nd4, Mt-Nd5 Mitochondrial subunits Nd2, Nd4, Nd5 encoding the NAD dehydrogenase (complex I), Muc1 Mucin 1, cellsurface associated, Myh7b Myosin heavy chain 7B, Myo5a:Myosin VA Myo7a Myosin VIIA, Myo9b Myosin IXB, Myo15a Myosin XVA, Myl4 Myosin, light chain 4, Ncf1 Neutrophil cytosolic factor 1 (encodes the 47-kilodalton cytosolic subunit of neutrophil NADPH oxidase), Ncf2 Neutrophil cytosolic factor 2 (=p67phox; 7-kilodalton cytosolic subunit of neutrophil NADPH oxidase), NCF4 Neutrophil cytosolic factor 4, 40 kDa, Ncr3 Natural cytotoxicity triggering receptor 3, Ndufa4 NADH dehydrogenase 1 alpha subcomplex 4, Ndufc2 NADH:ubiquinone oxidoreductase subunit C2, Nek8 NIMA-related kinase 8, Nfe2l2 Nuclear factor, erythroid 2 like 2 (=Nrf2), Ngly1 N-glycanase 1, Nlgn3 Neuroligin-3, Nlrp1 NLR family, pyrin domain containing 1, Nox4 NADPH oxidase 4, Nppa Natriuretic peptide A (=Anp), Nppb Natriuretic peptide B (=Bnp), Nppc Natriuretic peptide C (=Cnp), Npy Neuropeptide Y, Nr1i2 Nuclear receptor subfamily 1 group I member 2 (=Pxr, Pregnane X receptor), Nr1i3 Nuclear receptor subfamily 1 group I member 3 (=Car, Constitutive androstane receptor), Nr2f2 Nuclear receptor subfamily 2 group F member 2, Nr3c1 Nuclear receptor subfamily 3 group C member 1 (=Gr, Glucocorticoid receptor), Nrg1 Neuregulin 1, Nur4a1 Nuclear receptor subfamily 4 group A member 1 (=Nur77), Oca2 Oculocutaneous albinism II, Ogdh Oxoglutarate dehydrogenase, Ogn Osteoglycin, Oprl1 Opioid related nociceptin receptor 1 (nociceptin/orphanin FQ receptor), P2rx7 Purinergic receptor P2X7, P2ry14 Purinergic receptor P2Y14, Pappa1 Pappalysin 1, Pappa2 Pappalysin 2, Park7 Parkinson protein 7 (=Dj1), Pax6 Paired box 6, Pcdh15 Protocadherin 15, Pclo Piccolo presynaptic cytomatrix protein, Pde3a Phosphodiesterase 3A, Pde6b Phosphodiesterase 6B, Phkg2 Phosphorylase kinase, gamma 2 (testis), Pgls 6-phosphogluconolactonase, Phf24 PHD finger protein 24, Pi15 peptidase inhibitor 15, Pink1 Pten induced putative kinase, Pkhd1 Polycystic kidney and hepatic disease 1 (autosomal recessive), Plekha7 Pleckstrin homology domain containing family A member 7, Plekhm1 Pleckstrin homology domain containing, family M (with RUN domain) member 1, Plp1 Proteolipid protein 1, Pmch Pro-melanin-concentrating hormone, Pon1 Paraoxonase 1, Ppp4r3b Protein phosphatase 4 regulatory subunit 3B (=Smek2), Pparg Peroxisome proliferator activated receptor gamma, Prdm14 PR/SET domain 14, Prdx2 Peroxiredoxin 2, Prkdc Protein kinase, DNA-activated, catalytic polypeptide, Prkg2 Protein kinase, cGMP-dependent, type II, Prkn Parkin RBR E3 ubiquitin protein ligase (=Park2), Prlhr Prolactin releasing hormone receptor (=Gpr10), Prss8 Protease, serine, 8, Pten Phosphatase and tensin homolog, Ptprk Protein tyrosine phosphatase, receptor type, K, Rab38 RAB38, member RAS oncogene family, Rag1 Recombination activating gene 1, Rag2 Recombination activating gene 2, Rarres2 Retinoic acid receptor responder 2 (=chemerin), Rbm20 RNA binding motif protein 20, Rffl Ring finger and FYVE like domain containing E3 ubiquitin protein ligase (rififylin), Rffl-lnc1 Rffl-long non-coding RNA, RT1-A RT1 class I, locus A, Rin1 Ras and Rab interactor 1, RT1-Ba RT1 class II, locus Ba, RT1-Bb RT1 class II, locus Bb, Reln Reelin, Ren Renin, Resp18 Regulated endocrine-specific protein 18, Rgma Repulsive guidance molecule BMP co-receptor a, Rnaset2 Ribonuclease T2, Sbf1 SET binding factor 1, Scn1a Sodium channel, voltage-gated, type I, alpha subunit, Scn9a Sodium voltage-gated channel alpha subunit 9 (=Nav 1.7), Serpinc1 Serpin family C member 1 (=antithrombin III), Sh2b3 SH2B adaptor protein 3 (=Lnk), Shank2 SH3 and multiple ankyrin repeat domains 2, Shank3 SH3 and multiple ankyrin repeat domains 3, Shc1 SHC adaptor protein 1, Shroom3 Shroom family member 3, Slc6a3 Solute carrier family 6 member 3 (=DAT, dopamine transporter), Slc6a4 Solute carrier family 6 member 4 (= SERT, serotonin transporter), Slc11a2 Solute carrier family 11 (proton-coupled divalent metal ion transporter), member 2 (=Nramp2), Slc22a18 Solute carrier family 22, member 18, Slc39a12 Solute carrier family 39 member 12 (zinc transporter ZIP12), Slco1b2 Solute carrier organic anion transporter family member 1B2, SLCO1B3 Solute carrier organic anion transporter family member 1B3, Snca Synuclein alpha, Sod3 Superoxide dismutase 3, extracellular, Sorcs1 Sortilin-related VPS10 domain containing receptor 1, Sp6 Sp6 transcription factor, Spata22 Spermatogenesis associated 22, Stim1 Stromal interaction molecule 1, Sv2a synaptic vesicle glycoprotein 2A, Tap2 Transporter 2, ATP-binding cassette, sub-family B (MDR/TAP), Tbc1d1 TBC1 domain family member 1, Tbc1d4 TBC1 domain family member 4 (=As160), Tbx6 T-box 6, Tfr2 transferrin receptor 2, Themis Thymocyte selection associated, Tg Thyroglobulin, Tlr4 Toll-like receptor 4, Tmem63c Transmembrane protein 63c, Tmem67 Transmembrane protein 67 (=meckelin, Mks3), Tp53 Tumor protein 53, Tph2 Tryptophan hydroxylase 2, Tpcn2 Two pore segment channel 2, Trem2 Triggering receptor expressed on myeloid cells 2, Trpa1 transient receptor potential cation channel, subfamily A, member 1, Trpc4 Transient receptor potential cation channel, subfamily C, member 4, Trpc6 Transient receptor potential cation channel subfamily C member 6, Trpm4 Transient receptor potential cation channel subfamily M member 4, Trpv1 Transient receptor potential cation channel subfamily V member 1, Trpv3 Transient receptor potential cation channel, subfamily V, member 3, Trpv4 Transient receptor potential cation channel subfamily V member 4, Tsh Thyroid stimulating hormone receptor, Tspo Translocator protein, Tubb4a Tubulin beta 4A class Iva, Tyr Tyrosinase, Uba6 Ubiquitin-like modifier activating enzyme 6, Ubd Ubiquitin D (=Fat10), Ube3a Ubiquitin protein ligase E3A, Ugt1a1 UDP glycosyltransferase 1 family, member A1, Unc5c unc-5 netrin receptor 5 (=Unc5h3), Uox Urate oxidase, uricase, Vav1 Vav1 guanine nucleotide exchange factor, Vdr Vitamin D receptor, Vkorc1 Vitamin K epoxide reductase complex, subunit 1, Wars2 Tryptophanyl tRNA synthetase 2, mitochondrial, Wfs1 Wolframin ER transmembrane glycoprotein, Wwox WW domain-containing oxidase, Zbtb16 Zinc finger and BTB domain containing 16 (=Plzf)
  8. 2) Phenotypes and diseases: ADLTE Autosomal dominant lateral temporal lobe epilepsy, ADPKD Autosomal dominant polycystic kidney disease, AKI Acute kidney injury, ALSP Adult-onset leukoencephalopathy with axonal spheroid and pigmented glia, AMD Age-related macular degeneration, ARPKD Autosomal recessive polycystic kidney disease, CAKUT Congenital anomalies of the kidneys and the urinary tract, CDFE Cortical dysplasia-focal epilepsy, CV Cardiovascular, DJS Dubin-Johnson syndrome, EA2 Episodic ataxia type 2, EAE Experimental autoimmune encephalomyelitis, FHM1 Familial hemiplegic migraine type 1, HNPCC Hereditary non-polyposis colorectal cancer, HPS Hermansky-Pudlak syndrome, HTNB Hypertension with brachydactyly (autosomal dominant), IBD Inflammatory bowel disease, IFAP Ichthyosis follicularis, atrichia, and photophobia, LVH Left ventricular hypertrophy, LVM Left ventricular mass, PAH Pulmonary artery hypertension, PCH3 Pontocerebellar Hypoplasia type 3, PD Parkinson disease, PIA Pristane-induced arthritis, PKHD1 Polycystic kidney and hepatic disease 1, RA Rheumatoid arthritis, RV Right ventricular, SAME Syndrome of apparent mineralocorticoid excess, SCA6 Autosomal dominant spino-cerebellar ataxia 6, T1DM Type 1 diabetes mellitus (Insulin-dependent diabetes mellitus), T2DM Type 2 diabetes mellitus (Non-insulin-dependent diabetes mellitus), VKCFD2 Combined deficiency of vitamin K dependent clotting factors type 2, (X-)SCID (X-linked) severe combined immunodeficiency
  9. 3) Others: ACTH Adrenocorticotropic hormone, CaMK Ca2+/calmodulin-dependent protein kinase, CNS Central nervous system, CRISPR-Cas Clustered regularly interspaced short palindromic repeat, ERE estrogen-responsive-element, ENU N-ethyl-N-nitrosourea, eQTL Expression quantitative trait locus, FHH Fawn-hooded hypertensive, GLP1 Glucagon-like peptide 1, HDL High density lipoproteins, HPA Hypothalamus-pituitary-adrenal, HS Heterogeneous stock, Ig Immunoglobulins, IGF-1 Insulin-like growth factor-1, KO Knockout, LDL Low density lipoprotein, LEW Lewis, LH Lyon hypertensive, LOH Loss of heterozygosity, mTORC1 mTOR complex 1 (MTOR = mechanistic target of rapamycin kinase), MWF Munich Wistar Frömter, QTL Quantitative trait locus, SD Sprague-Dawley, SNP Single nucleotide polymorphism, SHR Spontaneously hypertensive rat, SHRSP Spontaneously hypertensive rat, stroke prone, SHRSR Spontaneously hypertensive rat, stroke resistant, SR Dahl salt-resistant, SS Dahl salt-sensitive, TNF Tumor necrosis factor, UTR Untranslated transcribed region, WT Wild-type, WKY Wistar-Kyoto, ZFN Zinc finger nuclease