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: 7715792
• 负责人: LARY C WALKER
• 金额: $ 3.56万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715792
• 关键词: Adult; Age-Months; Alzheimer' s Disease; Alzheimer' s disease model; Amyloid beta-Protein Precursor; Axon; Brain; Computer Retrieval of Information on Scientific Projects Database; Cytomegalovirus; Dendrites; Disease; Electrons; Evaluation; Fluorescence; Funding; Grant; Green Fluorescent Proteins; Institution; Localized; Microscopic; Neurons; Pathogenesis; Pathology; Platelet-Derived Growth Factor; Primates; Publications; Rattus; Research; Research Personnel; Resources; Rodent; Saimiri; Source; Subfamily lentivirinae; Transgenes; Transgenic Organisms; Ubiquitin; Ubiquitin C; United States National Institutes of Health; mature animal; neuronal cell body; nonhuman primate; promoter; tau Proteins; tau expression; transgene expression

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. Our studies focused on 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. We have shown that the ubiquitin C promoter produces consistently superior expression compared to the cytomegalovirus and platelet-derived growth factor promoters in adult rats. These findings were used to support the use of ubiquitin as the promoter in a new transgenic rat model of Alzheimer's disease (publications, below). Transgene expression of both green fluorescent protein and tau protein is localized primarily in neuronal somata, axons, and proximal dendrites, and remains intense up to 18 months of age in rats. We have also shown that tau expression can be similarly increased in squirrel monkeys. Finally, we recently completed dual fluorescence and immuno-electron microscopic evaluations of tau expression in rats. Our results show that enduring, focal expression of lentivirus-delivered transgenes is feasible in adult animals, presenting a unique opportunity to efficiently model AD pathogenesis in biologically advantageous species.

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