MOLECULAR GENETICS OF INHERITED RETINAL DISEASE

遗传性视网膜疾病的分子遗传学

• 批准号: 2391728
• 负责人: MICHAEL B GORIN
• 金额: $ 22.01万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2391728
• 关键词: RNase protection assay; albinism; artificial chromosomes; autosomal recessive trait; developmental genetics; fluorescent in situ hybridization; gene expression; gene mutation; gene rearrangement; genetic disorder; genetic mapping; genetic transcription; genetically modified animals; laboratory mouse; messenger RNA; molecular cloning; molecular genetics; northern blottings; nucleic acid sequence; oligonucleotides; phenotype; polymerase chain reaction; pulsed field gel electrophoresis; retina disorder; retinal pigment epithelium

The pearl mutation in the mouse causes an elevation of retinal scotopic sensitivity, similar to human congenital stationary nightblindness. This hypopigmentation condition is thought to be analogous to the Hermansky Pudlak syndrome, a form of human albinism associated with severe episodes of bleeding. A nondegenerative, autosomal recessive condition, the pearl mutation causes changes in the development of the cells in the retina as well as ongoing morphological and biochemical changes in the adult retina. We are using a combination of positional cloning approaches, including the construction of YAC and PAC contigs, cDNA selection and screening, and exon-trapping to isolate the causative gene. Once the gene responsible for pearl is identified, the structure and the expression of this gene will be determined. PCR-based assays will be developed to determine the involvement of this gene in human conditions. Transgenic and in vitro gene transfer experiments will attempt to reverse or arrest the effects of the original mutation. These studies will aid in our understanding of the development and function of the retina and possible causes of retinal disease.

小鼠中的珍珠突变导致视网膜苏格兰的升高 敏感性，类似于人类先天性固定夜总会。 这 不形成条件被认为与赫尔曼斯基类似 Pudlak综合征，一种与严重发作相关的人类白化病的形式 出血。 非平裁，常染色体隐性状况，珍珠 突变导致视网膜细胞发展的变化AS 以及成人视网膜的持续形态和生化变化。 我们正在使用位置克隆方法的组合，包括 YAC和PAC重叠群的构建，选择和筛选，以及 外显子捕获以隔离因果基因。 一旦基因负责 鉴定出珍珠，该基因的结构和表达将是 决定。 将开发基于PCR的分析以确定 该基因在人类条件下的参与。 转基因和体外基因 转移实验将试图逆转或阻止 原始突变。 这些研究将有助于我们理解 视网膜的发展和功能以及视网膜的可能原因 疾病。