Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa
Open Access
- 23 April 2002
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 99 (9) , 6328-6333
- https://doi.org/10.1073/pnas.082714499
Abstract
Rhodopsin is the G protein-coupled receptor that is activated by light and initiates the transduction cascade leading to night (rod) vision. Naturally occurring pathogenic rhodopsin (RHO) mutations have been previously identified only in humans and are a common cause of dominantly inherited blindness from retinal degeneration. We identified English Mastiff dogs with a naturally occurring dominant retinal degeneration and determined the cause to be a point mutation in the RHO gene (Thr4Arg). Dogs with this mutant allele manifest a retinal phenotype that closely mimics that in humans with RHO mutations. The phenotypic features shared by dog and man include a dramatically slowed time course of recovery of rod photoreceptor function after light exposure and a distinctive topographic pattern to the retinal degeneration. The canine disease offers opportunities to explore the basis of prolonged photoreceptor recovery after light in RHO mutations and determine whether there are links between the dysfunction and apoptotic retinal cell death. The RHO mutant dog also becomes the large animal needed for preclinical trials of therapies for a major subset of human retinopathies.Keywords
This publication has 58 references indexed in Scilit:
- Amplification and kinetics of the activation steps in phototransductionPublished by Elsevier ,2003
- Homozygous and heterozygous Gly-188-Arg mutation of the rhodopsin gene in a family with autosomal dominant retinitis pigmentosaOphthalmic Genetics, 2000
- A Novel Retinal Degeneration Locus Identified by Linkage and Comparative Mapping of Canine Early Retinal DegenerationGenomics, 1999
- Frequency of the codon 807 mutation in the cGMP phosphodiesterase beta-subunit gene in Irish setters and other dog breeds with hereditary retinal degenerationJournal of Heredity, 1999
- Molecular basis of dark adaptation in rod photoreceptorsEye, 1998
- Novel rhodopsin mutation in an autosomal dominant retinitis pigmentosa family: phenotypic variation in both heterozygote and homozygote Val137Met mutant patientsHuman Genetics, 1996
- Topographical regulation of cone and rod opsin genes: parallel, position dependent levels of transcriptionDevelopmental Brain Research, 1995
- Missense rhodopsin mutation in a family with recessive RPNature Genetics, 1994
- Autosomal Dominant Retinitis Pigmentosa Caused by the Threonine-17-Methionine Rhodopsin Mutation: Retinal Histopathology and ImmunocytochemistryExperimental Eye Research, 1994
- Molecular Analysis and Genetic Mapping of the Rhodopsin Gene in Families with Autosomal Dominant Retinitis PigmentosaGenomics, 1993