Pathogenesis of Ocular Albinism

描述(由申请人提供)：白化病意味着一组遗传性疾病 常见的眼部和通常是皮肤萎缩的疾病 色素沉着，并与严重的视觉疾病有关。眼球 1型白化病(网船-瀑布型)是最常见的眼部疾病 白化病。基因突变致眼部白化病发病机制的探讨 在OA1基因中，小鼠Oal基因产物将通过组合进行研究 细胞、分子生物学、遗传学和生化技术。在.期间 在未来五年的支持下，要实现的四个具体目标是： 1.确定OA1在色素细胞中的亚细胞分布以及何时 在非黑素细胞哺乳动物细胞和酵母菌中表达 酿酒。 2.阐明将Oal定向到其亚细胞目的地的序列和 它运输到那个目的地的路径。 3.检验有关OA1在脑内潜在亚细胞功能的假设 哺乳动物和以酵母为基础的模型系统。 4.确定与OA1相互作用的蛋白质。 重点将放在了解特定的突变如何导致 临床疾病OA1影响蛋白质的定位、运输和 函数引入到OAL中。这项工作将揭示 这种突变导致人类视力疾病的手段以及基本的 细胞生物学中的机制。

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.