FUNCTIONAL STUDIES OFNR2E3 IN RETINAL DEVELOPMENT

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The rd/rd7 mutant mice display retinal degeneration and have white, evenly spaced spots over their entire retina at one month of age and subsequently develop mottled retinal pigmentation and a 50% photoreceptor cell degeneration by 16 months of age. The rd7 mouse carries a mutation in the photoreceptor cell-specific nuclear receptor (NR2E3) gene. Mutations in the human NR2E3 gene are associated with a unique retinal dystrophy, Enhanced S Cone syndrome (ESCS). Most inherited human retinal diseases affect mature photoreceptor distribution by reducing the numbers of receptors in the mosaic through apoptotic mechanisms. A common finding is that disease-causing photoreceptor- specific genes alter key structures or functions within these cells that lead to cell death. ESCS is unique in that it manifests as greater numbers of a subtype of photoreceptors, showing a major increase in the least populous cone subtype, the S-cones; with varying degrees of retinal degeneration. The goal of this study is to functional characterize mNR2E3 and gain insight into mechanisms involved in the correct development and function of the retina. This goal will be accomplished by investigating the following aims: 1. determining the temporal and spatial expression pattern of NR2E3, 2. identifying factors that interact with NR2E3, and 3. identifying downstream effector genes.