Genetic Screen for Retinal Degeneration Mutants in Drosophila

果蝇视网膜变性突变体的遗传筛查

• 批准号: 8328619
• 负责人: FRANK LASKI
• 金额: $ 18.59万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8328619
• 关键词: Actin-Binding Protein; Adherens Junction; Age related macular degeneration; Apical; Apoptotic; Biological Process; Blindness; Cells; Classification; Data; Defect; Development; Disease; Drosophila eye; Drosophila genus; Drosophila melanogaster; Exploratory/Developmental Grant; Eye; Genes; Genetic; Genetic Screening; Goals; Grant; Homologous Gene; Human; Lead; Light; Membrane; Molecular; Mutation; Necrosis; Phenotype; Photoreceptors; Phototransduction; Physiological; Proteins; RNA Interference; Research Personnel; Research Project Grants; Retina; Retinal Degeneration; Retinal Diseases; Retinitis Pigmentosa; Role; Staging; Testing; Transport Vesicles; Vision; cofilin; fly; gene function; interest; mutant

DESCRIPTION (provided by applicant): Using a genetic approach with the fruit fly Drosophila melanogaster, we have found that the gene twinstar (tsr), which encodes the Drosophila homologue of the actin-binding protein cofilin/ADF, has a physiological role in the eye, as tsr has a light-dependent retinal degeneration (RD) mutant phenotype. We believe tsr represents a large group of genes that are required for viability that have an unidentified RD mutant phenotype. To test this, an RNAi screen for RD mutants in the fly was started. Preliminary data shows that this approach will be successful. The goal of this proposal is to screen 8,000 RNAi inducible lines for an RD mutant phenotype. Once identified, the new RD mutants will be characterized to determine the earliest visible defect in the retina, if the RD is light dependent, and if the degeneration is apoptotic or necrotic. There is significant overlap between RD genes in the fly and humans, indicating common function. Identifying additional Drosophila RD mutants will mark the human homologues as candidates for being associated with retinal diseases. It is also likely that many of the RD genes will have interesting biological functions in the Drosophila eye. Identifying these new RD genes will bring new researchers into the field of RD, leading to a better understanding of vision and retinal disease.

描述（由申请人提供）：使用果蝇果蝇的遗传方法，我们发现基因 twinstar (tsr) 编码肌动蛋白结合蛋白 cofilin/ADF 的果蝇同源物，在眼睛，因为 tsr 具有光依赖性视网膜变性 (RD) 突变表型。我们认为 tsr 代表了一大群具有未鉴定的 RD 突变表型的生存所需的基因。为了测试这一点，我们开始对果蝇中的 RD 突变体进行 RNAi 筛选。初步数据表明这种方法将会成功。该提案的目标是筛选 8,000 个 RNAi 诱导品系的 RD 突变表型。一旦鉴定出来，新的 RD 突变体将被表征，以确定视网膜中最早可见的缺陷，如果 RD 是光依赖性的，以及变性是否是细胞凋亡或坏死。果蝇和人类的 RD 基因之间存在显着重叠，表明具有共同的功能。鉴定其他果蝇 RD 突变体将把人类同源物标记为与视网膜疾病相关的候选者。许多 RD 基因也可能在果蝇眼睛中具有有趣的生物学功能。识别这些新的 RD 基因将使新的研究人员进入 RD 领域，从而更好地了解视力和视网膜疾病。