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Further insights into GPR179: Expression, localization, and associated pathogenic mechanisms leading to complete congenital stationary night blindness

AutorOrhan, Elise; Bhattacharya, Shom Shanker ; Zeitz, Christina
Palabras claveGPR179
Expression and localization
cCSNB
Pathogenicity
Trafficking defect
Mini-gene approach
Fecha de publicacióndic-2013
EditorAssociation for Research in Vision and Ophthalmology
CitaciónInvestigative Ophthalmology and Visual Science 54: 8041- 8050 (2013)
ResumenPurpose. Mutations in GPR179, which encodes the G protein-coupled receptor 179, lead to autosomal recessive complete (c) congenital stationary night blindness (CSNB), which is characterized by an ON-bipolar retinal cell dysfunction. This study further defined the exact site of Gpr179 expression and its protein localization in human retina and elucidated the pathogenic mechanism of the reported missense and splice site mutations. Methods. RNA in situ hybridization was performed with mouse retinal sections. A commercially available antibody was validated with GPR179-overexpressing COS-1 cells and applied to human retinal sections. Live-cell extracellular staining along with subsequent intracellular immunolocalization and ELISA studies were performed using mammalian cells overexpressing wild-type or missense mutated GPR179. Wild-type and splice site-mutated mini-gene constructs were transiently transfected, and RNA was extracted. RT-PCR-amplified products were cloned, and Sanger sequenced. Results. Mouse Gpr179 transcript was expressed in the upper part of the inner nuclear layer, and the respective human protein localized at the dendritic tips of bipolar cells in human retina. The missense mutations p.Tyr220Cys, p.Gly455Asp, and p.His603Tyr led to severely reduced cell surface localization, whereas p.Asp126His did not. The mutated splice donor site altered GPR179 splicing. Conclusions. Our findings indicate that the site of expression and protein localization of human and mouse GPR179 is similar to that of other proteins implicated in cCSNB. For most of the mutations identified so far, loss of the GPR179 protein function seems to be the underlying pathogenic mechanism leading to this form of cCSNB. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
DescripciónOrhan, Elise et al.
Versión del editorhttp://dx.doi.org/10.1167/iovs.13-12610
URIhttp://hdl.handle.net/10261/123123
DOI10.1167/iovs.13-12610
Identificadoresdoi: 10.1167/iovs.13-12610
issn: 0146-0404
e-issn: 1552-5783
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