biostudies-literatureNishiguchi KMMedical Research CouncilNational Institute for Health Research (NIHR)6006https://www.ebi.ac.uk/biostudies/studies/S-EPMC4354202biostudies-literatureUnknown6The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in Nature communicationsGene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179.PMC4354202NIHR-RP-011-003NF-SI-0513-10074MR/K025589/1MR/J005215/1Holthaus SMLuhmann UFRizzi MCarvalho LSAzam SADuran YRibeiro JBainbridge JWPowell KNishiguchi KMSmith AJAli RRfalseGene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179.The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in 2015-01-01T00:00:00Z2015 Jan2025-04-21T20:29:54.137Z2019-03-27T01:47:52ZS-EPMC43542022561332110.1038/ncomms7006