Behavioral Screen for Cone Mutations

视锥细胞突变的行为筛查

• 批准号: 6927799
• 负责人: Susan E Brockerhoff
• 金额: $ 30.32万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-13 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927799
• 关键词: autosomal recessive trait; behavior test; cone cell; electroretinography; gene mutation; genetic screening; histology; phenotype; retina; site directed mutagenesis; vision tests; visual pigments; zebrafish

DESCRIPTION (provided by applicant): Vertebrate cone photoreceptors are responsible for color and daytime vision. They have been extensively studied and much is known about their structure and function. For example, anatomical studies have described the morphologies of cone cells, the types of synpases they form and how they can adapt their shape in response to environmental and circadian factors. Furthermore, electrophysiological studies have described the physiological properties of cone responses to brief flashes of light and to steady illumination. Nevertheless there are many unanswered questions about cone structure and function. For example, although the physiological description of cone adaptation to illumination is well documented, the biochemical mechanism underlying this response is unknown. In addition, the mechanisms by which ribbon synapses form and are regulated are unknown. Finally many factors that influence cone photoreceptor shape and viability have yet to be discovered. In this proposal the investigators use zebrafish to identify genes essential for normal cone structure and function. The proposal relies heavily on the previous success of the investigator to identify genes essential for vertebrate cone function using a similar screening strategy. The specific aims of the proposal are: Specific Aim#l: Identify recessive mutations that are essential for normal cone photoreceptor function using an OKR behavioral screen followed by ERG analysis. Specific Aim#2: Perform histological analyses of the retinas of mutants with defects in cone photoreceptor function. Specific Aim #3: Identify the mutated genes by positional cloning and candidate gene analysis. All resources generated from this proposal will be made available to the scientific community. A specific plan for distributing the resources generated from this proposal has been designed with investigators at the zebrafish resource center in Oregon. This plan is presented as part of the proposal.

描述（由申请人提供）：脊椎动物锥体光感受器负责颜色和白天视觉。它们已经被广泛研究，并且对其结构和功能有很多了解。例如，解剖学研究描述了视锥细胞的形态、它们形成的突触类型以及它们如何根据环境和昼夜因素调整形状。此外，电生理学研究已经描述了视锥细胞对短暂闪光和稳定照明的反应的生理特性。然而，关于锥体的结构和功能还有许多未解之谜。例如，虽然锥适应照明的生理描述是有据可查的，这种反应背后的生化机制是未知的。此外，带状突触形成和调节的机制尚不清楚。最后，影响视锥细胞形状和生存能力的许多因素尚未被发现。在这项提议中，研究人员利用斑马鱼来鉴定正常视锥细胞结构和功能所必需的基因。该建议在很大程度上依赖于以前的成功，研究人员确定脊椎动物锥功能所必需的基因使用类似的筛选策略。具体目标#1：使用OKR行为筛选，然后进行ERG分析，鉴定对正常视锥光感受器功能至关重要的隐性突变。具体目标#2：对视锥光感受器功能缺陷的突变体的视网膜进行组织学分析。具体目标#3：通过定位克隆和候选基因分析来识别突变基因。该提案产生的所有资源都将提供给科学界。俄勒冈州的斑马鱼资源中心的调查人员已经设计了一个分配这一提议所产生的资源的具体计划。该计划是作为提案的一部分提出的。