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

PLoS Genetics
Lin LiJ Fielding Hejtmancik

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.

References

May 1, 1980·Journal of Neurophysiology·E A Newman
Jun 1, 1980·American Journal of Ophthalmology·E L BersonE Simonoff
Jul 1, 1994·Human Heredity·A A SchäfferR W Cottingham
Nov 23, 2006·Lancet·Dyonne T HartongThaddeus P Dryja
Mar 12, 2008·Archives of Ophthalmology·Motokazu TsujikawaYasuo Tano
Nov 26, 2008·Documenta Ophthalmologica. Advances in Ophthalmology·M F MarmorUNKNOWN International Society for Clinical Electrophysiology of Vision
Dec 2, 2008·Nature Reviews. Drug Discovery·Inki KimJohn C Reed
Sep 3, 2009·Visual Neuroscience·Ralph F Nelson, Nirmish Singla
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jan 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Magdy M MahfouzJian-Kang Zhu
Apr 5, 2011·American Journal of Human Genetics·Abel González-Pérez, Nuria López-Bigas
May 10, 2011·American Journal of Human Genetics·Goranka TanackovicCarlo Rivolta
Mar 8, 2012·Investigative Ophthalmology & Visual Science·Robert F MullinsEdwin M Stone
Mar 21, 2012·PloS One·Vishal M ShindeMarina S Gorbatyuk
May 17, 2012·Investigative Ophthalmology & Visual Science·Mansi M KunteMarina S Gorbatyuk
Sep 18, 2012·Progress in Retinal and Eye Research·Heidrun KuhrtHamid R Noori
Sep 25, 2012·Nature·Victoria M BedellStephen C Ekker
Oct 18, 2012·Investigative Ophthalmology & Visual Science·Heike KroegerJonathan H Lin
Jan 15, 2014·Human Molecular Genetics·Xue ChenChen Zhao
Feb 24, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yichang JiaSusan L Ackerman
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Apr 19, 2017·Investigative Ophthalmology & Visual Science·Lin LiJ Fielding Hejtmancik

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Citations

Oct 9, 2019·International Journal of Molecular Sciences·Frédéric Blond, Thierry Léveillard
Apr 4, 2021·Cells·Salvatore L StellaStephanie L Grillo

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Methods Mentioned

BETA
exome sequencing
Co-immunoprecipitation
transfection
genotyping
confocal microscopy
fluorescence microscopy
PCR
in vitro transcription
antisense oligonucleotides

Software Mentioned

Condel
ILINK
Lasergene
EMWIN
Polyphen2
SIFT
pcLink
BlastP
Blast
MLINK

Related Concepts

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Apoptosis

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