Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa.
PLoS Genet
; 14(8): e1007504, 2018 08.
Article
en En
| MEDLINE
| ID: mdl-30157172
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Retinitis Pigmentosa
/
Canales de Cloruro
/
Mutación Missense
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2018
Tipo del documento:
Article