UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Li, L; Jiao, X; D'Atri, I; Ono, F; Nelson, R; Chan, C-C; Nakaya, N; ... Hejtmancik, JF; + view all (2018) Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa. PLoS Genetics , 14 (8) , Article e1007504. 10.1371/journal.pgen.1007504. Green open access

[thumbnail of Lin Li_Mutation.pdf]
Preview
Text
Lin Li_Mutation.pdf - Published Version

Download (34MB) | Preview

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+/- 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.

Type: Article
Title: Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.1007504
Publisher version: https://doi.org/10.1371/journal.pgen.1007504
Language: English
Additional information: : This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 1.0 Universal (CC0 1.0) public domain dedication.
Keywords: Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, ISOLATED FROG RETINA, ENDOPLASMIC-RETICULUM, ER STRESS, GENE, DYSTROPHIES, ZEBRAFISH, DEGENERATION, EXPRESSION, ABCA4, DNA
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10056583
Downloads since deposit
25Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item