TY - JOUR
T1 - GPR179 Is Required for Depolarizing Bipolar Cell Function and Is Mutated in Autosomal-Recessive Complete Congenital Stationary Night Blindness
AU - Peachey, Neal S.
AU - Ray, Thomas A.
AU - Florijn, Ralph
AU - Rowe, Lucy B.
AU - Sjoerdsma, Trijntje
AU - Contreras-Alcantara, Susana
AU - Baba, Kenkichi
AU - Tosini, Gianluca
AU - Pozdeyev, Nikita
AU - Iuvone, P. Michael
AU - Bojang, Pasano
AU - Pearring, Jillian N.
AU - Simonsz, Huibert Jan
AU - van Genderen, Maria
AU - Birch, David G.
AU - Traboulsi, Elias I.
AU - Dorfman, Allison
AU - Lopez, Irma
AU - Ren, Huanan
AU - Goldberg, Andrew F. X.
AU - Nishina, Patsy M.
AU - Lachapelle, Pierre
AU - McCall, Maureen A.
AU - Koenekoop, Robert K.
AU - Bergen, Arthur A. B.
AU - Kamermans, Maarten
AU - Gregg, Ronald G.
PY - 2012
Y1 - 2012
N2 - 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 h-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
AB - 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 h-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
U2 - https://doi.org/10.1016/j.ajhg.2011.12.006
DO - https://doi.org/10.1016/j.ajhg.2011.12.006
M3 - Article
C2 - 22325362
SN - 0002-9297
VL - 90
SP - 331
EP - 339
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -