ISOLATION OF CONGENITAL STATIONARY NIGHT BLINDNESS GENES

先天性静止性夜盲症基因的分离

• 批准号: 2738393
• 负责人: RONALD G GREGG
• 金额: $ 16.39万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2738393
• 关键词: clinical research; congenital vision disorder; gene complementation; gene expression; gene mutation; genetic markers; genetic screening; genetically modified animals; genotype; human genetic material tag; in situ hybridization; laboratory mouse; linkage mapping; molecular cloning; neural transmission; night blindness; northern blottings; nucleic acid sequence; phenotype; polymerase chain reaction; restriction fragment length polymorphism; rod cell; sequence tagged sites; sex chromosomes; southern blotting; synapses

Identifying and characterizing the function of the numerous proteins that are required for normal visual function is an important goal in biomedical research. We describe a mutant mouse model whose phenotype mimics a human disease called congenital stationary night blindness (CSNB). The mouse mutation has been named nob because its electroretinogram has no b-wave. Our preliminary studies have localized the nob gene to the X-chromosome, in a region syntenic to that in humans that contains the genes responsible for CSNB1, CSNB2 and CSNB4, and two forms of retinitis pigmentosa (RP2 and RP3). The specific aims are: (1) localize the nob gene to a specific region on the X-chromosome, (2) identify the mouse nob gene by positional cloning and (3) determine if mutations in the human homologue of nob are responsible for eye disease. We hypothesize that the isolation and characterization of the mutation in this gene responsible for disrupting communication between the outer and inner retina will provide insight into the complex mechanism of synaptic transmission in the outer retina. Further, this mutant mouse will provide a model system in which to study gene therapy in the retina. The ultimate goal of these studies is to gain a more complete understanding of the mutation and its role in disrupting normal visual function, so that more targeted therapies can be devised to either cure or treat associated eye diseases.

鉴定和表征多种蛋白质的功能 是一个重要的目标， 生物医学研究 我们描述了一种突变小鼠模型，其表型 类似于一种叫做先天性静止性夜盲症的人类疾病 （CSNB）。 这种小鼠突变被命名为nob，因为它 视网膜电图没有b波。我们的初步研究已经定位了 将nob基因插入X染色体，位于与人类同线的区域 它包含负责CSNB1、CSNB2和CSNB4的基因， 视网膜色素变性（RP 2和RP 3）。 具体目标是：（1）将nob基因定位于特定区域 在X染色体上，（2）通过定位鉴定小鼠nob基因， 克隆和（3）确定NOB的人同源物中的突变是否 负责眼部疾病。 我们假设隔离和 表征该基因中负责破坏 外层和内层视网膜之间的沟通将提供洞察力 外层视网膜突触传递的复杂机制。 此外，这种突变小鼠将提供一个模型系统， 视网膜的基因治疗 这些研究的最终目的是 更全面地了解突变及其在 扰乱正常的视觉功能，这样更多的靶向治疗可以 被设计用于治愈或治疗相关的眼部疾病。