Grape polymers and neuroprotection

由于本提案中的项目重点涉及将转基因靶向血管细胞，我们提出了几种方法来产生特定部位和时间控制的转基因或突变事件。一个重点是利用DNA元件保护细胞特异性转基因表达，我们将利用Tie-2和SM22pha启动子分别在内皮和平滑肌中特异性表达。此外，所有五个项目都需要有条件地诱导转基因表达的能力，我们建议结合细胞特异性启动子、Cre重组酶和四环素诱导系统来随意激活转基因，或在特定时间诱导基因组中的突变。最后，对血管信号和血管生成过程中的基因功能的体内测试将使用小鼠损伤或疾病模型进行测试，这些模型是由这项赠款的参与者进行的。由于对颈动脉结扎模型、内皮剥脱模型和鳞癌模型的需求，这些将作为核心功能执行。

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.