Pathogenesis of Ocular Albinism

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DESCRIPTION (provided by applicant): Albinism connotes a group of genetic disorders that share in common the reduction of ocular and often cutaneous pigmentation, and are associated with significant visual morbidity. Ocular Albinism Type 1 (Nettleship-Falls type) is the most common form of ocular albinism. To understand the pathogenesis of ocular albinism caused by mutations in the OA1 gene, the murine Oal gene product will be studied by a combination of cellular, molecular biologic, genetic and biochemical techniques. During the next five years of support, the four specific aims to be pursued will be to: 1. Define the subcellular distribution of Oa1 in pigment cells and when expressed in nonmelanocytic mammalian cells as well as in Saccharomyces cerevisiae. 2. Elucidate the sequences that direct Oal to its subcellular destination and the pathway by which it traffics to that destination. 3. Test hypotheses regarding the potential subcellular function of Oa1 in mammalian and in yeast-based model systems. 4. Identify proteins that interact with Oa1. Emphasis will be placed on understanding how specific mutations causing the clinical disorder OA1 affect the protein's localization, trafficking and function when introduced into Oal. This work will shed light both upon the means by which such mutations cause human visual disease as well as upon basic mechanisms in cell biology.