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Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa.

Authors :
Li, Lin
Jiao, Xiaodong
D’Atri, Ilaria
Ono, Fumihito
Nelson, Ralph
Chan, Chi-Chao
Nakaya, Naoki
Ma, Zhiwei
Ma, Yan
Cai, Xiaoying
Zhang, Longhua
Lin, Siying
Hameed, Abdul
Chioza, Barry A.
Hardy, Holly
Arno, Gavin
Hull, Sarah
Khan, Muhammad Imran
Fasham, James
Harlalka, Gaurav V.
Source :
PLoS Genetics; 8/29/2018, Vol. 14 Issue 8, p1-29, 29p
Publication Year :
2018

Abstract

We identified a homozygous missense alteration (c.75C>A, p.D25E) in CLCC1, encoding a presumptive intracellular chloride channel highly expressed in the retina, associated with autosomal recessive retinitis pigmentosa (arRP) in eight consanguineous families of Pakistani descent. The p.D25E alteration decreased CLCC1 channel function accompanied by accumulation of mutant protein in granules within the ER lumen, while siRNA knockdown of CLCC1 mRNA induced apoptosis in cultured ARPE-19 cells. TALEN KO in zebrafish was lethal 11 days post fertilization. The depressed electroretinogram (ERG) cone response and cone spectral sensitivity of 5 dpf KO zebrafish and reduced eye size, retinal thickness, and expression of rod and cone opsins could be rescued by injection of wild type CLCC1 mRNA. Clcc1<superscript>+/-</superscript> KO mice showed decreased ERGs and photoreceptor number. Together these results strongly suggest that intracellular chloride transport by CLCC1 is a critical process in maintaining retinal integrity, and CLCC1 is crucial for survival and function of retinal cells. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15537390
Volume :
14
Issue :
8
Database :
Complementary Index
Journal :
PLoS Genetics
Publication Type :
Academic Journal
Accession number :
131482506
Full Text :
https://doi.org/10.1371/journal.pgen.1007504