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

2.50
Hdl Handle:
http://hdl.handle.net/11287/620835
Title:
Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa.
Authors:
Li, L. [et al]; Baple, Emma L.; Crosby, Andrew H.; Fasham, James
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.
Citation:
Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa. 2018, 14 (8):e1007504 PLoS Genet.
Publisher:
PLoS
Journal:
PLoS genetics
Issue Date:
Aug-2018
URI:
http://hdl.handle.net/11287/620835
DOI:
10.1371/journal.pgen.1007504
PubMed ID:
30157172
Additional Links:
http://dx.plos.org/10.1371/journal.pgen.1007504
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text.
Type:
Journal Article
Language:
en
ISSN:
1553-7404
Appears in Collections:
Clinical Genetics (Peninsula Genetics); Honorary contracts publications; 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, L. [et al]en
dc.contributor.authorBaple, Emma L.en
dc.contributor.authorCrosby, Andrew H.en
dc.contributor.authorFasham, Jamesen
dc.date.accessioned2018-10-02T13:37:26Z-
dc.date.available2018-10-02T13:37:26Z-
dc.date.issued2018-08-
dc.identifier.citationMutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa. 2018, 14 (8):e1007504 PLoS Genet.en
dc.identifier.issn1553-7404-
dc.identifier.pmid30157172-
dc.identifier.doi10.1371/journal.pgen.1007504-
dc.identifier.urihttp://hdl.handle.net/11287/620835-
dc.description.abstractWe 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.en
dc.language.isoenen
dc.publisherPLoSen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pgen.1007504en
dc.rightsArchived with thanks to PLoS geneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleMutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa.en
dc.typeJournal Articleen
dc.identifier.journalPLoS geneticsen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text.en
dc.type.versionPublisheden

Related articles on PubMed

All Items in RD&E Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.