Genetic studies on models of nuclear cataracts

核性白内障模型的遗传学研究

• 批准号: 7277190
• 负责人: D. J. SIDJANIN
• 金额: $ 32.44万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7277190
• 关键词: Biochemical; Biological Process; Blindness; Candidate Disease Gene; Cataract; Cell Nucleus; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 16; Chromosomes, Human, Pair 2; Cloning; Condition; Data Linkages; Development; Disease; Early Diagnosis; Environmental Exposure; Etiology; Exhibits; Family; Flecks; Gene Mutation; Genes; Genetic; Goals; Health behavior; Heterogeneity; Human; Human Chromosomes; Human Cloning; Individual; Inherited; Intervention; Knowledge; Lead; Lens Opacities; Location; Lod Score; Maps; Modeling; Molecular; Mus; Mutation; Nuclear; Operative Surgical Procedures; Other Therapy; Phenotype; Predisposition; Process; Reporting; Research Proposals; Synteny; Testing; base; blind; comparative; lens; lens transparency; novel

DESCRIPTION (provided by applicant): Cataracts, or lens opacities, are the leading cause of blindness worldwide. Cataracts are treatable with surgery, however, currently, no other therapies are available that could either inhibit, slow down, or reverse the development of cataracts. Therefore, it is necessary to expand our current knowledge of biological processes that lead to cataracts. The goals of this study are to develop mouse cataract models defined on molecular level that show how mutations in genes important for lens transparency correlate with functional, structural and biochemical abnormalities resulting in cataracts. This study focuses on two mouse cataract models of nuclear cataracts: coralliform cataract (Coc) is an autosomal dominant cataract that maps to 28.06 cM on mouse chromosome 16 in the region with synteny with HSA3q13-q21; lens opacity 4 (Lop4) is a semidominant nuclear cataract that maps to 96 cM on mouse chromosome 2 in the region of synteny with HSA20q11-q13. The specific aims of this study are: Specific Aim (1): Fine linkage map Coc and Lop4 loci to reduce the critical regions to < 1Mb. Specific Aim (2): Establish BAC minimal tiling path over Coc and Lop4 critical regions. Specific Aim (3): Identify and test positional candidate genes for causal association with the disease. Specific Aim (4): Once genes and mutations responsible for the Coc and Lop4 phenotypes are identified, the focus will be on characterizing the process of cataract development at the molecular level.

描述（由申请人提供）：白内障或镜头的不透明性是全球失明的主要原因。白内障可以通过手术治疗，但是，目前，没有其他疗法可以抑制，减慢或扭转白内障的发育。因此，有必要扩大我们当前对导致白内障的生物过程的了解。这项研究的目标是开发根据分子水平定义的小鼠白内障模型，该模型表明基因中对镜头透明度重要的突变与功能，结构和生化异常相关，从而导致白内障。 这项研究的重点是两个小鼠白内障模型的核白内障模型：Coralliform Cataract（COC）是 与HSA3Q13-Q21同步的该区域的小鼠染色体16小鼠染色体上的常染色体显性白内障。透镜不透明度4（LOP4）是一种半主导核白内障，在与HSA20Q11-Q13同步区域的小鼠染色体2上映射为96 cm。这项研究的具体目的是： 特定目的（1）：细细的链接图COC和LOP4基因座，将关键区域降低至<1MB。 具体目的（2）：在COC和LOP4关键区域上建立BAC最小平铺路径。 特定目的（3）：确定和测试与该病因果关系的位置候选基因。 具体目的（4）：一旦确定了COC和LOP4表型的基因和突变，重点将放在表征分子水平的白内障发育过程。