Table 3 Loss of NCL protein function in mammals and the effects on the expression, amounts, and activities of NCL genes/proteins

Loss of PPT1/CLN1 function

Sample

Affected gene/protein

Reference

Ppt1/Cln1^−/−

Brain tissues and cells from a Ppt1/Cln1^−/− mouse

Increased expression of CtsD/Cln10

Chandra et al., 2015 [87]

Ppt1/Cln1^−/−

Brain tissues and cells from a Ppt1/Cln1^−/− mouse

Reduced maturation of CTSD/CLN10 to its enzymatically active form

Chandra et al., 2015 [87]

Loss of TPP1/CLN2 function

Sample

Affected gene/protein

Reference

Tpp1/Cln2^−/−

Brain tissues from a Tpp1/Cln2^−/− mouse

Increased expression of CtsD/Cln10

Domowicz et al., 2019 [88]

Tpp1/Cln2^−/−

Brain tissues from a Tpp1/Cln2^−/− mouse

Increased expression of Pgrn/Cln11

Domowicz et al., 2019 [88]

Loss of CLN3 function

Sample

Affected gene/protein

Reference

CLN3 (mutated)

CLN3 disease patient fibroblasts

Reduced amount of PPT1/CLN1 in lysosomes, which correlated with reduced enzymatic activity

Appu et al., 2019 [89]

Cln3^Δex7/8

Mouse brain cortex from a Cln3^Δex7/8 mouse

Reduced amount of PPT1/CLN1 in lysosomes, which correlated with reduced enzymatic activity

Appu et al., 2019 [89]

Cln3^Δex7/8

Cerebellar cells from a Cln3^Δex7/8 mouse

Increased amount of PPT1/CLN1 in lysosomes, which correlated with increased enzymatic activity

Schmidtke et al., 2019 [90]

Cln3^Δex7/8

Cerebellar cells from a Cln3^Δex7/8 mouse

Increased amount of TPP1/CLN2 in lysosomes

Schmidtke et al., 2019 [90]

Cln3^Δex7/8

Cerebellar cells from a Cln3^Δex7/8 mouse

Decreased amount of CLN5 in lysosomes

Schmidtke et al., 2019 [90]

Cln3^Δex7/8

Cerebellar cells from a Cln3^Δex7/8 mouse

Decreased amount of CTSD/CLN10 in lysosomes

Schmidtke et al., 2019 [90]

Loss of DNAJC5/CLN4 function

Sample

Affected gene/protein

Reference

DNAJC5/CLN4 (mutated)

CLN4 disease patient brain

Increased amount of PPT1/CLN1

Henderson et al., 2016 [81]

DNAJC5/CLN4 (mutated)

CLN4 disease patient brain

Reduced enzymatic activity of PPT1/CLN1, which resulted in its mis-localization

Henderson et al., 2016 [81]

Loss of CLN5 function

Sample

Affected gene/protein

Reference

CLN5 (mutated)

CLN5 disease patient fibroblasts

Increased activity of TPP1/CLN2

Vesa et al., 2002 [77]

Loss of MFSD8/CLN7 function

Sample

Affected gene/protein

Reference

Mfsd8/Cln7^−/−

Embryonic fibroblasts from a Mfsd8/Cln7^−/− mouse

Reduced amount of CLN5 in lysosomes

Danyukova et al., 2018 [91]

Loss of PGRN/CLN11 function

Sample

Affected gene/protein

Reference

PGRN/CLN11 (heterozygous mutation)

FTD patient fibroblasts

Reduced activity of CTSD/CLN10

Ward et al., 2017 [92]

PGRN/CLN11 (heterozygous mutation)

FTD patient iPSC-derived cortical neurons

Reduced activity of CTSD/CLN10

Valdez et al., 2017 [80]

PGRN/CLN11^−/−

Liver, spleen, and brain samples from a PGRN/CLN11^−/−mouse

Reduced activity of CTSD/CLN10

Zhou et al., 2017 [79]

Loss of ATP13A2/CLN12 function

Sample

Affected gene/protein

Reference

ATP13A2/CLN12 knockdown

SH-SY5Y human neuroblastoma cells

Reduced amount and activity of CTSD/CLN10

Matsui et al., 2013 [93]