Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our recent analysis of gene expression led to the identification of several genes upregulated in endothelial cells that line tumor blood vessels, called Tumor endothelial markers (TEMs). Two of these, TEM5 and TEM8 are of particular interest because they reside on the cell surface and may therefore be directly accessible to blood-borne therapeutics. In an attempt to understand the functional role of TEM5 and TEM8 in angiogenesis, we have begun to generate TEM5 and TEM8 gene knockouts. Because these genes are also likely to be involved developmental angiogenesis we are generating conditional floxed alleles using cre/flp technology such that the gene can be disrupted specifically in adult tissues. By challenging gene disrupted mice with tumors, we hope to determine if either of these genes is critical for tumor angiogenesis. The studies should also allow us to better understand the function of these genes in angiogenesis.