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.