First Author | Okada Y | Year | 2008 |
Journal | Blood | Volume | 112 |
Issue | 6 | Pages | 2336-9 |
PubMed ID | 18519813 | Mgi Jnum | J:138735 |
Mgi Id | MGI:3806211 | Doi | 10.1182/blood-2008-01-135079 |
Citation | Okada Y, et al. (2008) A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo. Blood 112(6):2336-9 |
abstractText | We recently demonstrated that the 3-kb 5'-flanking region of the human ROBO4 gene directs endothelial cell-specific expression in vitro and in vivo. Moreover, a GA-binding protein (GABP)-binding motif at -119 was necessary for mediating promoter activity in vitro. The goal of the present study was to confirm the functional relevance of the -119 GABP-binding site in vivo. To that end, the Hprt locus of mice was targeted with a Robo4-LacZ transgenic cassette in which the GABP site was mutated. In other studies, the GABP mutation was introduced into the endogenous mouse Robo4 locus in which LacZ was knocked-in. Compared with their respective controls, the mutant promoters displayed a significant reduction in activity in embryoid bodies, embryos, and adult animals. Together, these data provide strong support for the role of the GABP-binding motif in mediating Robo4 expression in the intact endothelium. |