The Role of Nephrocystin-5 in Retinal Degeneration

Nephrocystin-5 在视网膜变性中的作用

• 批准号: 8543459
• 负责人: Cecinio Castillo Ronquillo
• 金额: $ 3.44万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8543459
• 关键词: Accounting; Affect; Carrier Proteins; Cell Culture System; Cell Polarity; Cells; Centrosome; Cilia; Clinical; Co-Immunoprecipitations; Cystic Kidney Diseases; Cytoplasm; Development; Diagnosis; Disease; Exons; Eye; Functional disorder; Gene Targeting; Genes; Genetic; Goals; In Vitro; Kidney; Knock-out; Lead; Leber' s amaurosis; Methods; Microtubule-Organizing Center; Modeling; Mus; Mutation; Nephronophthisis; Pathogenesis; Pathology; Pathway interactions; Patients; Pharmacological Treatment; Photoreceptors; Proteins; Research Project Grants; Retina; Retinal; Retinal Degeneration; Retinitis Pigmentosa; Rhodopsin; Role; Societies; Structure; Syndrome; System; Testing; cilium biogenesis; in vitro Model; in vivo; insight; kinetosome; matrigel; mouse model; photoreceptor degeneration; promoter; research study; retinal rods

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. ! !

描述（由申请人提供）：肾植物是一种遗传性囊性肾脏疾病。该疾病有许多外部表现。肾脏寄生虫最常见的病理之一是视网膜变性（视网膜炎色素炎或Leber先天性amurosis）。这项涉及肾脏和视网膜的临床发现被诊断为高级综合症。肾植物的发育主要归因于几种肾环囊蛋白蛋白的突变，这些突变被认为在细胞中原代纤毛的发育和正常功能中很重要。有趣的是，在几乎所有高年级综合征患者中都发现了NPHP5突变。但是，目前尚不知道NPHP5的正常功能以及NPHP5突变如何促进视网膜变性。该论文项目的目的是建立体内的体外模型，以研究NPHP5的正常作用，因为它与视网膜变性的发展有关。第一个目的是在小鼠的杆感光细胞中发展有条件的NPHP5，以了解该蛋白质的缺失可能导致色素性视网膜样视网膜样视网膜样变性的发展。第二个目的是研究NPHP5在控制细胞极性在体外细胞培养系统中的预测作用中的作用。呢呢