Behavioral Screen for Cone Mutations

视锥细胞突变的行为筛查

• 批准号: 7100120
• 负责人: Susan E Brockerhoff
• 金额: $ 29.61万
• 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/7100120
• 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）：脊椎动物视锥细胞负责颜色和白天视觉。它们已被广泛研究，并且对其结构和功能了解很多。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节律因素调整其形状。此外，电生理学研究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，关于视锥细胞的结构和功能，还有许多悬而未决的问题。例如，尽管视锥细胞适应光照的生理学描述已有充分记录，但这种反应背后的生化机制尚不清楚。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活力的许多因素尚未被发现。在这项提案中，研究人员使用斑马鱼来识别正常视锥细胞结构和功能所必需的基因。该提案在很大程度上依赖于研究人员之前使用类似筛选策略识别脊椎动物锥体功能必需基因的成功。该提案的具体目标是： 具体目标#1：使用 OKR 行为筛选和 ERG 分析来识别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：对锥体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将提供给科学界。俄勒冈州斑马鱼资源中心的研究人员已经设计了一个分配该提案产生的资源的具体计划。该计划作为提案的一部分提出。