Grape polymers and neuroprotection

葡萄聚合物和神经保护

• 批准号: 6383893
• 负责人: HELEN KIM
• 金额: $ 26.32万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6383893
• 关键词: alternative medicine; amyloid proteins; apoptosis; brain mapping; chemoprevention; flavonoids; genetically modified animals; immunochemistry; laboratory mouse; laboratory rat; mass spectrometry; microtubules; neuritic plaques; neuroprotectants; oxidative stress; pharmacokinetics; plant extracts; tissue /cell culture

As the focus of the projects in this proposal involve targeting of transgenes to vascular cells, we propose several approaches to generate site-specific and temporally controlled transgenes or mutational events. One focus is to use DNA elements coffering cell-specific transgene expression, and we will utilize tie-2, and SM22alpha promoters to specify expression in endothelium and smooth muscle, respectively. In addition, all five projects require the ability to induce transgene expression in a conditional manner, and we propose the combination of cell specific promoters, the Cre-recombinase, and the tetracycline inducible systems to either activate transgenes at will, or induce mutations in the genome at specific times. Finally, in vivo tests of gene function during vascular signaling and angiogenesis will be tested using murine injury or disease models which have been performed by participants in this grant. Because of the demand for the carotid ligation model, endothelial scrape denudation, and squamous cell carcinoma models, these will be performed as core functions.

作为该提案中项目的重点涉及将转基因靶向血管细胞，我们提出了几种产生特定地点和时间控制的转基因或突变事件的方法。一种重点是使用辅助细胞特异性转基因表达的DNA元素，我们将使用TIE-2和SM22Alpha启动子分别指定内皮和平滑肌的表达。此外，所有五个项目都要求能够以条件方式诱导转基因表达，我们提出了细胞特异性启动子，CRE结构酶和四环素诱导系统的组合，以随意激活转基因，或在特定时间诱导基因组中的突变。最后，将使用该赠款中参与者进行的鼠损伤或疾病模型对血管信号传导和血管生成过程中基因功能的体内测试进行测试。由于对颈动脉连接模型的需求，内皮刮擦剥离和鳞状细胞癌模型，这些模型将作为核心功能进行。