The Role of Nephrocystin-5 in Retinal Degeneration

描述（由申请人提供）：肾病是一种遗传性囊性肾病。这种疾病有许多外部表现。肾炎最常见的相关病理之一是视网膜变性（色素性视网膜炎或Leber先天性黑朦）的发展。这一临床表现累及肾脏和视网膜，诊断为老年洛肯综合征。肾病的发展主要归因于几种肾囊素蛋白的突变，这些蛋白被认为在细胞初级纤毛的发育和正常功能中很重要。有趣的是，NPHP5突变几乎在所有老年loken综合征患者中都被发现。然而，目前尚不清楚NPHP5的正常功能以及NPHP5突变如何导致视网膜变性。本论文项目的目标是建立体内和体外模型，研究NPHP5在视网膜变性发展中的正常作用。第一个目标是在小鼠的杆状光感受器细胞中开发一种条件敲除NPHP5的方法，以了解缺乏该蛋白如何导致色素性视网膜变性样视网膜变性的发展。第二个目的是研究NPHP5在体外细胞培养系统中控制细胞极性的预测作用。！ ！

DESCRIPTION (provided by applicant): Nephronophthisis is a genetic cystic kidney disease. There are numerous extrarenal manifestations of the disease. One of the most common associated pathologies of nephronophthisis is the development of retinal degeneration (Retinitis Pigmentosa or Leber Congenital Amaurosis). This clinical finding involving the kidneys and the retina is given the diagnosis of Senior-Loken syndrome. Development of nephronophthisis has been attributed primarily to mutations in several nephrocystin proteins, which are thought to be important in the development and normal function of the primary cilium in cells. Interestingly, mutations in NPHP5 have been found in virtually all Senior-Loken syndrome patients. However, it is still currently not known what the normal function of NPHP5 and how NPHP5 mutations contribute to retinal degeneration. The goal of this thesis project is to establish both in vivo an in vitro models to study the normal role of NPHP5 as it relates to development of retinal degeneration. The first aim is to develop a conditional knock out of NPHP5 in rod photoreceptor cells of mice to understand how absence of the protein may lead to development of retinitis pigmentosa-like retinal degeneration. The second aim is to investigate the role of NPHP5 in its predicted role of controlling cellular polarity in an in vitro cell culture system. ! !