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）：利用果蝇黑腹果蝇的遗传方法，我们发现编码肌动蛋白结合蛋白cofilin/ADF的果蝇同源基因twinstar （tsr）在眼睛中具有生理作用，因为tsr具有光依赖性视网膜变性（RD）突变表型。我们认为tsr代表了具有未知RD突变表型的生存能力所需的一大组基因。为了验证这一点，开始了对果蝇RD突变体的RNAi筛选。初步数据表明，这种方法将是成功的。本提案的目标是筛选8000个RNAi诱导系的RD突变表型。一旦确定，新的RD突变体将被表征，以确定视网膜中最早的可见缺陷，RD是否依赖于光，以及变性是否为凋亡或坏死。果蝇和人类的RD基因有明显的重叠，表明功能相同。确定更多的果蝇RD突变体将标志着人类同源物作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。发现这些新的RD基因将为RD领域带来新的研究人员，从而更好地了解视力和视网膜疾病。