Models for Vision Research

视觉研究模型

基本信息

  • 批准号:
    8266455
  • 负责人:
  • 金额:
    $ 98.27万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-05-01 至 2015-04-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Approximately 50 million people worldwide are blind and ~150 million are significantly vision impaired. Except for trauma and infections, the majority of human eye diseases are genetic in nature. The number of human loci causing retinal disease is ~ 9-fold greater than the number of available associated animal models, indicating a large gap in models for studying diseases that are known to occur in humans. The mouse with its well-developed genetics, similarity to human physiology and anatomy, and accessibility for genetic manipulation is a widely accepted and useful model system. Mouse models have been used to provide candidate genes for human diseases, tissues for study throughout development and disease progression, and test systems for therapies. They are also an ideal platform to identify and dissect biologically relevant pathways through genetic means. In the last funding cycle, we generated >60 models with ocular defects. We have identified the molecular basis of 20 of the mutant lines from which many unique insights were obtained. In this application, we plan to complete the molecular and phenotypic characterization of the 40 remaining lines (Aim 1) and make them available to the scientific research community. Extending our ongoing genetic studies, we propose to use a sensitized chemical mutagenesis screen to reveal pathways important in the Crumbs1 pathway (Aim 2). While there are many strategies available to identify interacting factors of primary genes/mutations, chemically induced mutations have the advantage that they will allow for the unbiased identification of a wide array of genes that interact with CRUMBS1. These genes may explain the plethora of diseases associated with mutations within Crumbs1. It will also allow for identification of factors that interact with the extracellular domain of CRUMBS1, an endeavor that has been intractable by the current available methods. In the present application, we will screen ~10,000 mutagenized G3 Crumbs1rd8/rd8 mice by indirect ophthalmoscopy to identify mutants that present with an altered Crumbs1drd8 fundus phenotype. The molecular bases of these factors will be identified and through the use of standard immunohistochemical methodologies in conjunction with the use of 4Pi microscopy, we will examine the effects of the newly identified genes/mutations on the CRUMBS1 pathway. Successful conclusion of this proposal will not only generate well characterized ocular models, but will potentially identify entry points into the CRUMBS1 pathways as well as other molecules that are important in eye biology and afford us the opportunity to build and test hypotheses about normal ocular function and disease pathology.
项目摘要/摘要 全球约有5000万人失明,约1.5亿人视力严重受损。 除了创伤和感染,大多数人类眼部疾病本质上都是遗传的。数量 导致视网膜疾病的人类基因座比现有相关动物模型的数量多出约9倍, 这表明,在研究已知发生在人类身上的疾病的模型方面存在很大差距。带着它的鼠标 发达的遗传学,与人类生理和解剖学的相似性,以及遗传的可及性 操纵是一个被广泛接受和有用的模型系统。鼠标模型已经被用来提供 人类疾病的候选基因,在整个发育和疾病进展过程中研究的组织,以及 测试治疗系统。它们也是识别和剖析生物相关性的理想平台 通过遗传手段的途径。 在上一个资助周期中,我们制作了60个眼睛缺陷的模型。我们已经确定了分子 20个突变系的基础上,从中获得了许多独特的见解。在此应用程序中,我们计划 完成其余40个品系的分子和表型特征(目标1),并使它们 可供科学研究界使用。 扩展我们正在进行的基因研究,我们建议使用一种敏化的化学诱变筛选来 揭示在Crums1途径中重要的途径(目标2)。虽然有许多策略可用来 识别主要基因/突变的相互作用因素,化学诱导突变的优点是 它们将允许无偏见地识别与CRUMBS1相互作用的广泛基因。这些 基因可能解释了与Crums1基因突变相关的过多疾病。它还将允许 鉴定与CRUMBS1胞外结构域相互作用的因子,这项工作已经 用目前可用的方法是难以治愈的。在本申请中,我们将筛选~10,000个诱变者 用间接眼底镜检查G3Crums1rd8/Rd8小鼠以鉴定存在Crums1drd8改变的突变体 眼底表型。这些因子的分子基础将被鉴定,并通过使用标准 免疫组织化学方法结合4PI显微镜的使用,我们将检查其效果 新发现的CRUMBS1途径上的基因/突变。 这一提议的成功结束不仅将产生具有良好特征的眼睛模型,而且还将 潜在地识别进入CRUMBS1途径的入口点以及其他在 眼生物学,并为我们提供了建立和测试关于正常眼功能和 疾病病理学。

项目成果

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Patsy M Nishina其他文献

Patsy M Nishina的其他文献

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{{ truncateString('Patsy M Nishina', 18)}}的其他基金

Genetic Modifiers of Retinal Disease
视网膜疾病的基因修饰
  • 批准号:
    10375022
  • 财政年份:
    2022
  • 资助金额:
    $ 98.27万
  • 项目类别:
Genetic Modifiers of Retinal Disease
视网膜疾病的基因修饰
  • 批准号:
    10574542
  • 财政年份:
    2022
  • 资助金额:
    $ 98.27万
  • 项目类别:
The Laboratory Mouse in Vision Research II
视觉研究 II 中的实验室小鼠
  • 批准号:
    7114208
  • 财政年份:
    2006
  • 资助金额:
    $ 98.27万
  • 项目类别:
Models for Vision Research
视觉研究模型
  • 批准号:
    7887712
  • 财政年份:
    2005
  • 资助金额:
    $ 98.27万
  • 项目类别:
Models for Vision Research
视觉研究模型
  • 批准号:
    7057224
  • 财政年份:
    2005
  • 资助金额:
    $ 98.27万
  • 项目类别:
Models for Vision Research
视觉研究模型
  • 批准号:
    7687175
  • 财政年份:
    2005
  • 资助金额:
    $ 98.27万
  • 项目类别:
Models for Vision Research
视觉研究模型
  • 批准号:
    8536463
  • 财政年份:
    2005
  • 资助金额:
    $ 98.27万
  • 项目类别:
Models for Vision Research
视觉研究模型
  • 批准号:
    8050064
  • 财政年份:
    2005
  • 资助金额:
    $ 98.27万
  • 项目类别:
Models for Vision Research
视觉研究模型
  • 批准号:
    7217859
  • 财政年份:
    2005
  • 资助金额:
    $ 98.27万
  • 项目类别:
Models for Vision Research
视觉研究模型
  • 批准号:
    7616705
  • 财政年份:
    2005
  • 资助金额:
    $ 98.27万
  • 项目类别:

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