GPR179 Is Required for Depolarizing Bipolar Cell Function and Is Mutated in Autosomal-Recessive Complete Congenital Stationary Night Blindness
- Authors
- 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.
- ID
- ZDB-PUB-120215-13
- Date
- 2012
- Source
- American journal of human genetics 90(2): 331-339 (Journal)
- Registered Authors
- Bergen, Arthur A.B., Gregg, Ronald G., Kamermans, Maarten
- Keywords
- none
- 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
- PubMed
- 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.