Retinal Degeneration is Accelerated when a Mutant Rhodopsin Transgene is Expressed on a Haploid or Null Rhodopsin Background
The rod opsin Pro23His mutation accounts for approximately 12% of autosomal dominant retinitis pigmentosa (adRP) cases in the United States. To study mechanisms leading to photoreceptor degeneration, we investigated the effects of mutant and wild-type opsin stoichiometry on retinal morphology and function. We crossbred a trans-genic mouse line expressing the triple mutant, V20G, P23H, and P27L (GHL), with rhodopsin knockout mice. Retinal morphology of 30-day old GHL+ mice with two functional copies of the rod opsin gene (GHL+, rho+/+), one functional copy (GHL+, rho+/−) or no functional copies of the rod opsin gene (GHL+, rho−/−) was examined. Although mice of all three genotypes underwent reunal degeneration, the severity of the retinopathy correleted inversely with the number of wild-type opsin genes present. Mice with no functional wild-type opsin gene were most severely affected, while those with two functional copies were the least affected. Mice with a single functional vvild-type gene were intermediate in the degenerative phenotype. Correspondingly, changes in fundus morphology and ERG function. were most prominent in GHL+, rho−/− mice, whereas GHL+, rho−/− mice were similar to wild-type mice.
KeywordsRetinitis Pigmentosa Retinal Degeneration Outer Nuclear Layer Opsin Gene Functional Copy
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