| First Author | Minami T | Year | 2002 |
| Journal | Blood | Volume | 100 |
| Issue | 12 | Pages | 4019-25 |
| PubMed ID | 12393668 | Mgi Jnum | J:80525 |
| Mgi Id | MGI:2446010 | Doi | 10.1182/blood-2002-03-0955 |
| Citation | Minami T, et al. (2002) Differential regulation of the von Willebrand factor and Flt-1 promoters in the endothelium of hypoxanthine phosphoribosyltransferase-targeted mice. Blood 100(12):4019-25 |
| abstractText | An important limitation of standard transgenic assays is that multiple copies of the transgene are inserted randomly into the mouse genome, resulting in line-to-line variation in expression. One way to control for these variables is to target a single copy of the transgene to a defined locus of the mouse genome by homologous recombination. In the present study, we have used such an approach to target the promoters of 2 different genes, namely von Willebrand factor (VWF) and Flt-1, to the hypoxanthine phosphoribosyltransferase (Hprt) gene locus. Consistent with previous findings in standard transgenic animals, we report that the VWF promoter contains information for expression in a subset of endothelial cells in the heart, skeletal muscle, and brain. In contrast, the Flt-1 promoter directs expression in all vascular beds except for the liver. The Flt-1 transgene was active in the endothelium of tumor xenografts, whereas the VWF promoter was not. Under in vitro conditions, conditioned medium from tumor cells resulted in a significant up-regulation of Flt-1 mRNA and promoter activity, but no change in VWF levels. Taken together, these results suggest that (1) Hprt locus targeting is a valuable tool for studying vascular bed-specific gene regulation, (2) the VWF and Flt-1 promoters are regulated by distinct transcriptional mechanisms in the intact endothelium, and (3) tumor angiogenesis results in the differential activation of endothelial cell-specific promoters. |
