GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness.
Animals, Chromosome Mapping, Dark Adaptation, Electroretinography, Gene Knockdown Techniques, 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
Am J Hum Genet 2012 Feb 10; 90(2):331-9.
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.
Peachey, Neal S; Ray, Thomas A; Florijn, Ralph; Rowe, Lucy B; Sjoerdsma, Trijntje; Contreras-Alcantara, Susana; Baba, Kenkichi; Tosini, Gianluca; Pozdeyev, Nikita; Iuvone, P Michael; Bojang, Pasano; Pearring, Jillian N; Simonsz, Huibert Jan; van Genderen, Maria; Birch, David G; Traboulsi, Elias I; Dorfman, Allison; Lopez, Irma; Ren, Huanan; Goldberg, Andrew F X; Nishina, Patsy M; Lachapelle, Pierre; McCall, Maureen A; Koenekoop, Robert K; Bergen, Arthur A B; Kamermans, Maarten; and Gregg, Ronald G, "GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness." (2012). Faculty Research 2012. 76.