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PHOTORECEPTOR MUTATIONS

光感受器突变

基本信息

批准号：
6627060
负责人：
Susan E Brockerhoff
金额：
$ 20.34万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
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

项目摘要

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.

细胞的组织和组成的研究视网膜提供了一种对人类如何将其视觉化的理解环境和治愈人类视网膜疾病所需的框架。然而，关于脊椎动物视网膜功能的许多问题仍然存在。无人接听。例如，尽管中涉及的许多组件锥体感光细胞的光反应已经被识别出来，精确的这些分子定义视锥细胞生理功能的机制与杆状生理学不同的是，目前尚不清楚。此外，尽管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，很少有这样的分子被鉴定出来。识别细胞- 特定类型的分子将回答关于形成的两个问题视网膜内的特定连接以及关于建立细胞类型的地位和身份。这项提议的目标是使用斑马鱼突变体来回答这些问题问题。我们已经开发了一种行为测试，可以有效地识别视网膜有细微和特定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以了解脊椎动物的视网膜功能。2)我们将描述利用生化、分子和生理手段详细分析突变情况接近了。我们将首先关注三个突变。其中两个， NOA和NRB导致视锥感光细胞生理异常，以及第三个突变，pob，导致红锥的选择性丧失。视网膜内的光感受器。我们的描述将有助于定义视锥细胞感光细胞的生理反应。3.)我们还将使用用于识别红色敏感锥体特异性分子的POB突变光感受器。4)。最后，我们将定义分子的性质利用候选基因或位置检测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数据库，并绘制这些基因的图谱。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Retinal disease in vertebrates.

脊椎动物的视网膜疾病。

DOI：
10.1016/s0079-6123(01)31049-x
发表时间：
2001
期刊：
Progress in brain research
影响因子：
0
作者：
Brockerhoff,SE
通讯作者：
Brockerhoff,SE

A zebrafish model for pyruvate dehydrogenase deficiency: rescue of neurological dysfunction and embryonic lethality using a ketogenic diet.

DOI：
10.1073/pnas.0307074101
发表时间：
2004-03
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Michael R. Taylor;J. Hurley;H. V. Van Epps;Susan E. Brockerhoff
通讯作者：
Michael R. Taylor;J. Hurley;H. V. Van Epps;Susan E. Brockerhoff

Investigations of photoreceptor synaptic transmission and light adaptation in the zebrafish visual mutant nrc.

斑马鱼视觉突变体 nrc 光感受器突触传递和光适应的研究。