P23H Rhodopsin Mutant Swine Model of Reninitis Pigmentosa

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DESCRIPTION (provided by applicant): Retinal degeneration is a leading cause of blindness in the Western world and retinitis pigmentosa (RP) is the most common cause of hereditary visual loss in adult life. Although the genetic basis of RP has been well explored, the translation of this insight into successful genetic therapy has been hindered because of the mutational heterogeneity that underlies this group of diseases. In addition to gene therapy, we and others are exploring alternative therapeutic approaches employing recent advances in stem cell therapy, as well as the retinal prosthesis, bioengineering and pharmacology. Together these hold the promise for successful neural reconstitution in RP. Using the method of single cell nuclear transfer, we produced six male miniature swine (mini-swine) on a NIH cc haplotype carrying a mutant Pro23His (P23H) human rhodopsin transgene at the National Swine Resource Research Center at the University of Missouri-Columbia. Our preliminary data show that these founders exhibited an electrophysiologic phenotype characteristic of RP. Since P23H is the most common autosomal dominant mutation responsible for RP in man, we propose to establish a colony and characterize three independent transgenic lines of this new mini-swine model of photoreceptor degeneration. While outside the time frame of this application, in the near future it can be used by us and the vision community for novel therapeutic interventions. PUBLIC HEALTH RELEVANCE: Using the method of single cell nuclear transfer, we produced six male miniature swine (mini-swine) on a NIH cc haplotype carrying a mutant Pro23His (P23H) human rhodopsin transgene at the National Swine Resource Research Center at the University of Missouri-Columbia. Our preliminary data show that these founders exhibited an electrophysiologic phenotype characteristic of retinitis pigmentosa (RP). Since P23H is the most common autosomal dominant mutation responsible for RP in humans, we propose to establish a colony and characterize three independent transgenic lines of this new mini-swine model of photoreceptor degeneration for future therapeutic interventions.