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GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness.

Complete congenital stationary night blindness (cCSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impairment of night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual functions. We report here that mutations in GPR179, encoding an orphan G protein receptor, underlie a form of autosomal-recessive cCSNB. The Gpr179(nob5/nob5) mouse model was initially discovered by the absence of the ERG b-wave, a component that reflects depolarizing bipolar cell (DBC) function. We performed genetic mapping, followed by next-generation sequencing of the critical region and detected a large transposon-like DNA insertion in Gpr179. The involvement of GPR179 in DBC function was confirmed in zebrafish and humans. Functional knockdown of gpr179 in zebrafish led to a marked reduction in the amplitude of the ERG b-wave. Candidate gene analysis of GPR179 in DNA extracted from patients with cCSNB identified GPR179-inactivating mutations in two patients. We developed an antibody against mouse GPR179, which robustly labeled DBC dendritic terminals in wild-type mice. This labeling colocalized with the expression of GRM6 and was absent in Gpr179(nob5/nob5) mutant mice. Our results demonstrate that GPR179 plays a critical role in DBC signal transduction and expands our understanding of the mechanisms that mediate normal rod vision.

Pubmed ID: 22325362

Authors

  • Peachey NS
  • Ray TA
  • Florijn R
  • Rowe LB
  • Sjoerdsma T
  • Contreras-Alcantara S
  • Baba K
  • Tosini G
  • Pozdeyev N
  • Iuvone PM
  • Bojang P
  • Pearring JN
  • Simonsz HJ
  • van Genderen M
  • Birch DG
  • Traboulsi EI
  • Dorfman A
  • Lopez I
  • Ren H
  • Goldberg AF
  • Nishina PM
  • Lachapelle P
  • McCall MA
  • Koenekoop RK
  • Bergen AA
  • Kamermans M
  • Gregg RG

Journal

American journal of human genetics

Publication Data

February 10, 2012

Associated Grants

  • Agency: NEI NIH HHS, Id: P30 EY006360
  • Agency: NCI NIH HHS, Id: P30CA34196
  • Agency: NEI NIH HHS, Id: P30EY006360
  • Agency: NEI NIH HHS, Id: R01 EY004864
  • Agency: NEI NIH HHS, Id: R01 EY014701
  • Agency: NEI NIH HHS, Id: R01 EY016501
  • Agency: NEI NIH HHS, Id: R01EY004864
  • Agency: NEI NIH HHS, Id: R01EY014701
  • Agency: NEI NIH HHS, Id: R01EY016501
  • Agency: NEI NIH HHS, Id: R01EY020821
  • Agency: NEI NIH HHS, Id: R01EY12354
  • Agency: NINDS NIH HHS, Id: R01NS43459
  • Agency: NEI NIH HHS, Id: R21 EY021852-01
  • Agency: NEI NIH HHS, Id: R21EY021852
  • Agency: NCRR NIH HHS, Id: RR017890
  • Agency: Canadian Institutes of Health Research, Id:

Mesh Terms

  • Animals
  • Chromosome Mapping
  • Dark Adaptation
  • Electroretinography
  • Eye Diseases, Hereditary
  • Gene Knockdown Techniques
  • Genetic Diseases, X-Linked
  • Heterozygote
  • Humans
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mutation
  • Myopia
  • Night Blindness
  • Pedigree
  • Receptors, G-Protein-Coupled
  • Receptors, Metabotropic Glutamate
  • Retinal Bipolar Cells
  • Retinal Rod Photoreceptor Cells
  • Signal Transduction
  • Zebrafish