TRANSDUCTION AND RETINAL DEGENERATION IN DROSOPHILA

果蝇的转导和视网膜变性

• 批准号: 2467534
• 负责人: PATRICK J. DOLPH
• 金额: $ 17.98万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2467534
• 关键词: Drosophilidae; SDS polyacrylamide gel electrophoresis; alleles; arrestins; electrophysiology; gene induction /repression; gene mutation; genetic mapping; immunocytochemistry; laboratory rabbit; molecular cloning; nucleic acid sequence; phosphorylation; protein structure function; retina degeneration; rhodopsin; visual phototransduction

DESCRIPTION (Adapted from applicant's abstract): While not identical to vertebrate systems, Drosophila phototransduction is similar in several respects, and the power of the genetic system justifies its use as a model. Extensive genetic screens have been conducted by this applicant for genes that can affect the rate of retinal degeneration which follows from altered rhodopsin:arrestin ratios. In all, 350,000 F1 flies screened have yielded 112 new dominant mutations. This innovative approach stands in contrast to the huge effort required to discover phototransduction mutants directly by their ERG phenotypes. There are four specific aims. In the first aim, the applicant will study the ten new arrestin alleles in the collection by determining the null ERG phenotype, and examining the role of phosphorylation, rhodopsin binding and the function of the arrestin C-terminal domain. The second aim focuses on the ten new rhodopsin mutants that cause retinal degeneration, some of which do so in a novel light-dependent manner. The third aim involves the molecular isolation and characterization of a new retinal degeneration locus recovered four times in the screen. The fourth aim is to pursue the characterization of the other mutations recovered in the screens.

描述（改编自申请人摘要）：虽然与 在脊椎动物系统中，果蝇的光转导在几个方面是相似的。 尊重，和遗传系统的力量证明它作为一个模型的使用。 本申请人已进行了广泛的基因筛选， 这会影响视网膜变性的速度， 视紫红质：抑制蛋白比率。 总共筛选了35万只F1果蝇， 112个新的显性突变。 这种创新的方法与 直接发现光转导突变体所需的巨大努力， 他们的ERG表型。 有四个具体目标。 在第一个目标中， 申请人将通过以下方式研究该集合中的10个新的抑制蛋白等位基因： 确定无效ERG表型，并检查 磷酸化，视紫红质结合和抑制蛋白的功能 C-末端结构域。 第二个目标集中在十个新的视紫红质突变体 会导致视网膜退化，其中一些会在小说中 光依赖的方式。 第三个目标涉及分子分离， 一个新的视网膜变性位点的特征恢复了四次， 屏幕 第四个目的是追求他者的特征化 在筛选中恢复的突变。