Behavioral Screen for Cone Mutations

描述(申请人提供)：脊椎动物视锥感光细胞负责颜色和日间视觉。人们对它们进行了广泛的研究，对它们的结构和功能也有了很多了解。例如，解剖学研究描述了锥体细胞的形态，它们形成的突触的类型，以及它们如何适应环境和昼夜因素的形状。此外，电生理学研究已经描述了锥体对短暂的闪光和稳定的光照反应的生理特性。然而，关于锥体的结构和功能仍有许多悬而未决的问题。例如，尽管锥体对光照适应的生理学描述已经被很好地记录下来，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，影响视锥体光感受器形状和活性的许多因素尚未被发现。在这项研究中，研究人员使用斑马鱼来识别正常视锥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的成功，即使用类似的筛选策略来识别脊椎动物锥体功能所必需的基因。该提案的具体目标是：特定目标#L：使用OKR行为筛查识别对正常视锥体光感受器功能至关重要的隐性突变，然后进行视网膜电图分析。具体目标#2：对视锥感光细胞功能缺陷突变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。这项提案产生的所有资源都将提供给科学界。俄勒冈州斑马鱼资源中心的调查人员已经设计了一个具体的计划来分配这项提案产生的资源。该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.