GPR179 Is Required for Depolarizing Bipolar Cell Function and Is Mutated in Autosomal-Recessive Complete Congenital Stationary Night Blindness

Peachey, N.S., Ray, T.A., Florijn, R., Rowe, L.B., Sjoerdsma, T., Contreras-Alcantara, S., Baba, K., Tosini, G., Pozdeyev, N., Iuvone, P.M., Bojang, P., Pearring, J.N., Simonsz, H.J., van Genderen, M., Birch, D.G., Traboulsi, E.I, Dorfman, A., Lopez, I., Ren, H., Goldberg, A.F., Nishina, P.M., Lachapelle, P., McCall, M.A., Koenekoop, R.K., Bergen, A.A., Kamermans, M., and Gregg, R.G.
American journal of human genetics   90(2): 331-339 (Journal)
Registered Authors
Bergen, Arthur A.B., Gregg, Ronald G., Kamermans, Maarten
MeSH Terms
  • Animals
  • Chromosome Mapping/methods
  • Dark Adaptation/genetics
  • Electroretinography/methods
  • Eye Diseases, Hereditary
  • Gene Knockdown Techniques/methods
  • Genetic Diseases, X-Linked
  • Heterozygote
  • Humans
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mutation*
  • Myopia/genetics*
  • Myopia/metabolism
  • Myopia/physiopathology*
  • Night Blindness/genetics*
  • Night Blindness/metabolism
  • Night Blindness/physiopathology*
  • Pedigree
  • Receptors, G-Protein-Coupled/genetics*
  • Receptors, Metabotropic Glutamate/genetics
  • Retinal Bipolar Cells/metabolism*
  • Retinal Bipolar Cells/physiology*
  • Retinal Rod Photoreceptor Cells/metabolism
  • Retinal Rod Photoreceptor Cells/physiology
  • Signal Transduction
  • Zebrafish
22325362 Full text @ Am. J. Hum. Genet.

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 Gpr179nob5/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 Gpr179nob5/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.

Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes