PHOTORECEPTOR MUTATIONS

光感受器突变

• 批准号: 2739205
• 负责人: Susan E Brockerhoff
• 金额: $ 15.74万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2739205
• 关键词: color visions; cone cell; cryopreservation; electroretinography; gene expression; gene mutation; genetic library; genetic polymorphism; genetic screening; high performance liquid chromatography; immunocytochemistry; in situ hybridization; information systems; light adaptations; linkage mapping; molecular cloning; polymerase chain reaction; retinal adaptation; scintillation counter; visual photoreceptor; visual phototransduction; visual pigments; zebrafish

Investigations of the cellular organization and composition of the retina have provided an understanding of how humans visualize their surroundings and a framework necessary to cure human retinal diseases. Nevertheless, many questions about vertebrate retinal function remain unanswered. For example, although many of the components involved in cone photoreceptor light responses have been identified, the precise mechanisms by which these molecules function to define cone physiology as distinct from rod physiology are unclear. Also, although different cone types in the vertebrate retina are thought likely to express unique molecules, few such molecules have been identified. Identifying cell- type specific molecules would answer questions both about the formation of specific connections within the retina and questions about the establishment of cell-type position and identity. The goal of this proposal is use zebrafish mutants to answer these questions. We have developed a behavioral assay that efficiently identifies zebrafish mutants with subtle and specific defects in retinal function. 1). We will continue to isolate more mutations as a resource for understanding vertebrate retinal function. 2) We will characterize mutations in detail using biochemical, molecular and physiological approaches. We will focus initially on three mutations. Two of these, noa and nrb, produce abnormalities in cone photoreceptor physiology, and the third mutations, pob, causes the selective loss of red cone photoreceptors within the retina. Our characterization will help define the physiological responses of cone photoreceptors. 3.) We will also use the pob mutation to identify molecules specific to red-sensitive cone photoreceptors. 4). Finally, we will define the molecular nature of the defect in noa, nrb and pob by using a candidate gene or positional cloning approach. As a first step towards this end, we will generate a database of retina-specific genes and map these genes.

细胞组织和组成的研究， 视网膜提供了一个了解人类如何看待他们的眼睛。 治疗人类视网膜疾病所必需的环境和框架。 然而，关于脊椎动物视网膜功能的许多问题仍然存在， 无人回应例如，尽管涉及的许多组件 锥光感受器光反应已经被确定，精确的 这些分子的作用机制决定了视锥细胞的生理机能 与视杆生理学的区别尚不清楚。此外，虽然不同 脊椎动物视网膜中的视锥类型被认为可能表达独特的 分子，很少有这样的分子已被确定。识别细胞- 类型特异性分子可以回答关于 视网膜内的特定连接以及关于 确定细胞类型位置和身份。 这项提议的目的是用斑马鱼突变体来回答这些问题 问题.我们开发了一种行为检测方法， 识别视网膜神经元特异性缺陷的斑马鱼突变体 功能1）。我们将继续分离更多的突变作为资源 来了解脊椎动物的视网膜功能。2)我们将描述 使用生物化学、分子和生理学方法， 接近。我们将首先关注三个突变。其中两个， NOA和NRB在视锥光感受器生理学中产生异常， 第三个突变，POB，导致红锥细胞的选择性丢失， 视网膜内的光感受器。我们的描述将有助于定义 视锥光感受器的生理反应。3.）第三章我们还将使用 POB突变以鉴定对红色敏感视锥细胞特异性分子 光感受器4）。最后，我们将定义的分子性质的 通过使用候选基因或定位基因检测NOA、NRB和POB缺陷 克隆方法作为实现这一目标的第一步，我们将生成一个 视网膜特异性基因的数据库，并绘制这些基因。