Mouse models of human retinal disease caused by expression of mutant rhodopsin. A valuable tool for the assessment of novel gene therapies.

Abstract

The genetic basis for a wide range of inherited retinal diseases has been identified in recent years. To date, over 118 retinal disease loci have been mapped, for which 55 genes have been isolated (Clarke et al. 2000). Of these diseases, inherited photoreceptor degenerations represent a significant proportion of diseases that cause serious visual impairments in individuals of all ages and ethnic backgrounds (Berson 1996). While most forms of photoreceptor degeneration are characterized by rod and/or cone dysfunction, individual subtypes are further classified based on the type of inheritance, pattern of visual loss, appearance of the retina, and the gene defect causing these symptoms (Dryja et al. 1990b; Berson 1996; Wang et al. 2001). One of the most prominent genes that has been shown to cause progressive photoreceptor degeneration when mutated, is the rhodopsin gene. Patients carrying a number of different mutations in rhodopsin have displayed clinical symptoms of retinitis pigmentosa, varying in the severity of visual impairment (Dryja et al. 1990a; Dryja et al. 1990b; Dryja et al. 1991).