TRANSGENIC EXPRESSION OF TAU AND APP IN MODELS OF ALZHEIMER'S DISEASE

TAU 和 APP 在阿尔茨海默病模型中的转基因表达

• 批准号: 7562655
• 负责人: LARY C WALKER
• 金额: $ 3.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562655
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein Precursor; Brain; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Funding; Genes; Grant; Green Fluorescent Proteins; Human; Human Pathology; Incubated; Institution; Modeling; Pathology; Primates; Proteins; Rat-1; Rattus; Research; Research Personnel; Resources; Rodent; Saimiri; Source; Tauopathies; Transgenes; Transgenic Organisms; United States National Institutes of Health; aged; nonhuman primate; protein expression; tau Proteins; tau expression; tau mutation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The focus of this project was interactions between tau protein and the amyloid precursor protein (APP) in producing Alzheimer's disease pathology in the rodent (rat) and nonhuman primate (Saimiri sciureus) brain, with particular emphasis on tau protein in primates. These proteins are known to be critical to the development of Alzheimer's disease, but the existing models do not fully mimic the uniquely human pathology of Alzheimer's. We confirmed the long-term expression of the protein GFP in rats ( 1 year) as well as the induction of tau abnormalities by the protein. Genes for human-type tau protein are currently incubating in Saimiri, and we expect to have the results by early summer. We began an analysis of tau protein abnormalities in aged nonhuman primates to assess the natural occurrence of this pathology and its similarities to human tauopathies. Significant progress was made in developing a construct that enables the simultaneous expression of two separate transgenes.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的重点是tau蛋白和淀粉样前体蛋白（APP）之间的相互作用，在啮齿动物（大鼠）和非人灵长类动物（松鼠猴）大脑中产生阿尔茨海默病病理学，特别强调灵长类动物中的tau蛋白。已知这些蛋白质对阿尔茨海默病的发展至关重要，但现有的模型并不能完全模拟阿尔茨海默病独特的人类病理学。 我们证实了GFP蛋白在大鼠中的长期表达（1年）以及该蛋白对tau异常的诱导。人类型tau蛋白的基因目前正在Saimiri孵化，我们希望在初夏之前得到结果。我们开始分析老年非人灵长类动物的tau蛋白异常，以评估这种病理学的自然发生及其与人类tau蛋白病的相似性。在开发能够同时表达两个单独的转基因的构建体方面取得了重大进展。