Behavioral Screen for Cone Mutations

描述（申请人提供）：脊椎动物的视锥细胞负责颜色和白天的视觉。人们对它们进行了广泛的研究，对它们的结构和功能也了解得很多。例如，解剖学研究描述了锥体细胞的形态，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仍有许多未解之谜。例如，尽管视锥细胞适应光照的生理描述已被充分记录，但这种反应背后的生化机制尚不清楚。此外，带状突触形成和调控的机制尚不清楚。最后，许多影响视锥光感受器形状和活力的因素尚未被发现。在这项提议中，研究人员使用斑马鱼来识别正常锥体结构和功能所必需的基因。该建议在很大程度上依赖于研究者先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行为筛查和ERG分析确定对正常锥体感光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鉴定突变基因。本提案产生的所有资源将提供给科学界。俄勒冈斑马鱼资源中心的研究人员已经设计了一项分配该提案产生的资源的具体计划。这个计划是作为提案的一部分提出的。

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.