GENETICS OF MACULAR DEGENERATION

黄斑变性的遗传学

• 批准号: 7123290
• 负责人: KANG ZHANG
• 金额: $ 13.97万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123290
• 关键词: angiogenesis; biochemistry; clinical research; electroretinography; gene expression; genetically modified animals; genetics; histology; human subject; immunoelectron microscopy; laboratory mouse; linkage mapping; macular degeneration; macular drusen; messenger RNA; northern blottings; polymerase chain reaction; protein localization; protein structure function

DESCRIPTION (provided by applicant): The broad objective of this proposal is to identify a disease gene responsible for North Carolina macular dystrophy and to elucidate the underlying molecular mechanisms that lead to macular degeneration. North Carolina macular dystrophy (OMIM #136550) is an autosomal dominant, highly penetrant macular degeneration characterized by variable phenotypes including confluent drusen in the macula, macular atrophy, and choroidal neovascularization. Three specific aims are designed to test the underlying central hypothesis: that the protein product of the gene for North Carolina macular dystrophy, designated as MCDR1, is essential for the normal function of the macula and that the macular degeneration phenotype is associated with mutations in the MCDR1 gene. The three specific aims are: 1) to identify the disease gene for North Carolina Macular Dystrophy, MCDR1; 2) to characterize the mRNA and protein expression profiles and function of MCDR1; 3) to study the biological effect of MCDR1 in a mouse system. It is important to study the genetic basis of North Carolina macular dystrophy, as it causes juvenile macular degeneration with visual loss. Furthermore, North Carolina macular dystrophy shares important clinical features with age-related macular degeneration (AMD). Drusen is a hallmark of AMD and choroidal neovascularization (CNV) is one of the most important complications of AMD. Both of them are present in patients with North Carolina macular dystrophy. Therefore, these observations make North Carolina macular dystrophy a unique genetic model for AMD. Understanding the molecular mechanisms of MCDR1 should lead to novel insights into the pathogenesis of macular degeneration. Elucidation of the function of the MCDR1 gene may increase our understanding of retinal cell biology in general and drusen formation in particular. Finally, this study may provide information for pursuing novel strategies for treatment of macular degeneration.

描述（由申请人提供）：本提案的主要目的是确定导致北卡罗来纳黄斑营养不良的疾病基因，并阐明导致黄斑变性的潜在分子机制。北卡罗莱纳黄斑营养不良（omim# 136550）是一种常染色体显性、高渗透的黄斑变性，其特征是多种表型，包括黄斑汇合性囊肿、黄斑萎缩和脉络膜新生血管。