16 Models, Mutants, and Man: Searching for Unique Phenotypes and Genes in the Dog Model of Inherited Retinal Degeneration

Abstract

The past 15 years has seen a virtual explosion of gene and phenotype discovery in medical ophthalmology. Since the mapping of an autosomal dominant retinitis pigmentosa (ADRP) locus to the long arm of human chromosome 3 in the region of the rhodopsin (RHO) gene (McWilliam et al. 1989; Farrar et al. 1990), and the subsequent identification of the first disease-associated mutation (Dryja et al. 1990), there has been very rapid progress in identification of multiple loci and genes that are responsible for inherited visual dysfunction or blindness occurring alone or as part of more complex syndromes. Approximately 150 retinal disease loci have been mapped to date; of these, disease-causing mutations have been found in approximately 100 genes (Fig. 1; http://www.sph.uth.tmc.edu/RetNet/). Even for the RHO gene, over 100 disease-causing mutations have been identified, and, although most are inherited as autosomal dominant (AD) and cause RP, autosomal recessive RP (ARRP) and AD congenital stationary nightblindness (CSNB) forms also are recognized (Rivolta et al. 2002). Thus, allelic and genetic heterogeneity are the rule when considering the inherited diseases of the retina. Despite this complexity, rapid progress has been possible because of the very thorough earlier studies that critically defined the phenotypic characteristics of many of these disorders in man (for review, see Berson 1993; see also Berson et al. 1968, 1969; Kemp et al. 1988; Cideciyan and Jacobson 1993; Jacobson et al. 1994).

Dogs also suffer from various forms of inherited retinal blindness, the principal one termed progressive retinal atrophy (PRA). This is...