Pathogenesis of Ocular Albinism

描述（由申请人提供）：白化病意味着一组遗传性 这些疾病的共同点是眼部和皮肤的 色素沉着，并与显着的视觉发病率。眼部 白化病1型（Nettleship-Falls型）是最常见的眼部 白化病了解突变引起的眼白化病的发病机制 在OA 1基因中，鼠Oa 1基因产物将通过组合 细胞、分子生物学、遗传学和生物化学技术。期间 在今后五年的支助工作中，要实现的四个具体目标是： 1.定义Oa 1在色素细胞中的亚细胞分布， 在非黑素细胞哺乳动物细胞以及酵母中表达 啤酒。 2.阐明将Oal导向其亚细胞目的地的序列， 它到达目的地的路径。 3.关于Oa 1在人乳腺癌中的潜在亚细胞功能的检验假设 哺乳动物和基于酵母的模型系统中。 4.识别与Oa 1相互作用的蛋白质。 重点将放在理解特定的突变是如何导致 临床疾病OA 1影响蛋白质的定位，运输和 函数时引入Oal。这项工作将揭示双方在 这种突变导致人类视觉疾病的方式以及基本的 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.