| First Author | Minami T | Year | 2003 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 23 |
| Issue | 11 | Pages | 2041-7 |
| PubMed ID | 12893685 | Mgi Jnum | J:127987 |
| Mgi Id | MGI:3765301 | Doi | 10.1161/01.ATV.0000089326.63053.9A |
| Citation | Minami T, et al. (2003) Ets motifs are necessary for endothelial cell-specific expression of a 723-bp Tie-2 promoter/enhancer in Hprt targeted transgenic mice. Arterioscler Thromb Vasc Biol 23(11):2041-7 |
| abstractText | OBJECTIVE: Tie-2 is an endothelial cell-specific receptor tyrosine kinase that is involved in the remodeling of blood vessels and angiogenesis. Our goal was to characterize Tie-2 promoter function as a means of providing insight into the mechanisms of endothelial cell-specific gene regulation. METHODS AND RESULTS: When targeted to the Hprt locus of mice, a small Tie-2 promoter fragment (containing a 300-bp intronic enhancer coupled upstream to a 423-bp core promoter) (T-short) directed widespread endothelial cell expression in vivo. The T-short promoter contains 2 clusters of Ets sites, one in the first exon, the other in the intronic enhancer. In cultured endothelial cells, a combined mutation of the Ets motifs resulted in a significant reduction in promoter activity. Consistent with these results, the same Ets mutations resulted in a loss of detectable expression of the T-short promoter in all vascular beds with the notable exception of the brain. CONCLUSIONS: These results suggest that the T-short promoter contains information for widespread expression in the vascular tree, Ets sites are necessary for in vivo promoter activity, and the shorter Tie-2 fragment may be useful as a tool to direct heterologous gene expression within the intact endothelium. |
