Models for Vision Research

视觉研究模型

基本信息

  • 批准号:
    8536463
  • 负责人:
  • 金额:
    $ 25.53万
  • 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.
项目概要/摘要 全球约有 5000 万人失明,约 1.5 亿人视力严重受损。 除外伤和感染外,大多数人类眼部疾病本质上都是遗传性的。数量 导致视网膜疾病的人类基因座数量比现有相关动物模型数量多约 9 倍, 这表明研究已知人类疾病的模型存在巨大差距。鼠标与它的 发达的遗传学、与人类生理学和解剖学的相似性以及遗传的可及性 操纵是一种广泛接受且有用的模型系统。鼠标模型已被用来提供 人类疾病的候选基因、整个发育和疾病进展研究的组织,以及 治疗测试系统。它们也是识别和剖析生物学相关的理想平台 通过遗传手段的途径。 在上一个融资周期中,我们生成了超过 60 个具有眼部缺陷的模型。我们已经鉴定出分子 20 个突变系的基础,从中获得了许多独特的见解。在这个应用程序中,我们计划 完成剩余 40 个品系的分子和表型表征(目标 1)并使它们成为 可供科学研究界使用。 扩展我们正在进行的基因研究,我们建议使用敏化化学诱变筛选 揭示 Crumbs1 通路中的重要通路(目标 2)。虽然有很多策略可用于 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 它们将能够公正地识别与 CRUMBS1 相互作用的各种基因。这些 基因可以解释与 Crumbs1 突变相关的大量疾病。它还将允许 鉴定与 CRUMBS1 胞外域相互作用的因子,这一努力已被 目前可用的方法难以解决。在本申请中,我们将筛选约 10,000 个诱变的 G3 Crumbs1rd8/rd8 小鼠通过间接检眼镜检查来鉴定具有改变的 Crumbs1drd8 的突变体 眼底表型。这些因素的分子基础将被识别并通过使用标准 免疫组织化学方法结合 4Pi 显微镜的使用,我们将检查效果 CRUMBS1 通路上新发现的基因/突变。 该提案的成功完成不仅将产生特征良好的眼部模型,而且将 潜在地识别 CRUMBS1 途径的入口点以及其他重要的分子 眼生物学,使我们有机会建立和测试有关正常眼功能的假设 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:
    $ 25.53万
  • 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:
    $ 25.53万
  • 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:
    $ 25.53万
  • 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:
    $ 25.53万
  • 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:
    $ 25.53万
  • 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:
    $ 25.53万
  • 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:
    $ 25.53万
  • 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:
    $ 25.53万
  • 项目类别:
Models for Vision Research
视觉研究模型
  • 批准号:
    8266455
  • 财政年份:
    2005
  • 资助金额:
    $ 25.53万
  • 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:
    $ 25.53万
  • 项目类别:

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