Transgenic Animal Studies of Human Retinal Disease Caused by Mutations in Peripherin/RDS

Abstract

The photoreceptor disk membrane protein peripherin/rds is essential for the outer segment morphogenesis and integrity. Peripherin/rds associates with itself and with its homologue Rom-1 to form homo- and hetero-complexes, which are necessary for its structural role (Goldberg et al., 1995; Molday, 1998). More than seventy different pathogenic mutations in the peripherin/rds gene have been identified. These mutations are divided primarily into two categories: those associated with classic retinitis pigmentosa (RP), and those associated with various forms of macular dystrophy (MD). In fact, mutations in peripherin/rds account for 5–10% of RP causes, and is a major cause for MD (Kohl et al., 1998; Molday, 1998; http://www.sph.uth.tmc.edu/RetNet; http://www.retina-international.org/scinews/rdsmut.htm). Insights into the functional significance, structural role, and pathogenic effects of this protein have been accumulating considerably since its initial description; this is largely accomplished by the use of laboratory animal models. Use of transgenic or knock-out animals holds great potential for the investigation of retinal disease pathogenesis and the exploration of therapeutic interventions. Table 21.1 summarizes the animal models used to investigate the disease-causing mutations in peripherin/rds. In addition to the pathogenesis study, transgenic mouse and Xenopus laevis expressing the wild type peripherin/rds or the C-terminus have also been used to explore the structural and functional significance of the protein (Loewen et al., 2003; Ritter et al., 2004).