ANIMAL MODELS OF AGING IN RETINAL DEGENERATION

视网膜变性衰老的动物模型

• 批准号: 2633336
• 负责人: MELVIN SIMON
• 金额: $ 38.32万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-10 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2633336
• 关键词: aging; cell differentiation; cone cell; disease /disorder model; genetic manipulation; genetic promoter element; genetically modified animals; growth factor; laboratory mouse; model design /development; photobiology; reporter genes; retina degeneration; rod cell

The retina provides an ideal system in which to examine the nature of the mechanisms involved in late onset degenerative diseases that may be related to aging. A great deal is known about the biochemistry involved in the photoreceptor cascade that converts light to electrical signals and there is a great deal known about the structure of the retina and its development and differentiation. By using transgenic animals in the past four years we have developed lines of animals that express dominant mutant forms of components of the phototransduction cascade and studied the effects of these mutations on photoreceptor function and on retinal degeneration. These systems provide us with an opportunity to examine the effects of aging on comprised retinal systems and compare these models with late onset retinal degeneration disease. In continuing this project, we will generate more sophisticated mouse models by using homologous recombination to disrupt and replace genes encoding specific major components of the phototransduction cascade and by using cell type specific promoters to generate reporter systems that respond to growth and differentiation factors in the retina. In addition to defining the role of the components of the phototransduction cascade in maintaining cells in the retina, we will also study the effects of growth factors on retinal cell differentiation and maintenance. We will use transplantation and transgenic techniques to generate animals that have cells that secrete different growth factors at different stages during retinal development and to study the effects of these factors on the degeneration and differentiation. In addition, we will use transgenic mice and the reporter group s that we developed in order to transplant cells into the retinas of new born and eventually mature animals in order to try to ameliorate the effects of retinal degeneration.

视网膜提供了一个理想的系统，可以在其中检查 可能是晚期发作退行性疾病的机制 与衰老有关。 关于涉及的生物化学的了解很大 在光感受器的级联反应中，将光转换为电信号 关于视网膜及其的结构有很多了解 发展与分化。 过去使用转基因动物 四年我们已经开发出表达主导性的动物线 光转导级联的组件的突变形式并研究 这些突变对感光器功能和视网膜的影响 退化。 这些系统为我们提供了检查的机会 衰老对视网膜系统的影响并比较这些 具有延迟发作视网膜变性疾病的模型。 继续这样做 项目，我们将通过使用来生成更复杂的鼠标模型 同源重组以破坏和替换编码特定的基因 光转导级联的主要组成部分和使用细胞类型 特定的促进者生成响应增长的记者系统 和视网膜中的分化因子。 除了定义 光转移级联的组成部分在维护中的作用 视网膜中的细胞，我们还将研究生长因子对 视网膜细胞分化和维护。 我们将使用 移植和转基因技术生成具有的动物 在不同阶段分泌不同生长因子的细胞 视网膜发展并研究这些因素对 变性和分化。 此外，我们将使用转基因 我们为移植而开发的小鼠和记者组S 细胞进入新出生和最终成熟动物的视网膜 试图改善视网膜变性的影响。