Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice

Tissue-specific gene inactivation using the Cre-loxP system has become an i mportant tool to unravel functions of genes when the conventional null muta tion is lethal. We report here the generation of a transgenic mouse line ex pressing Cre recombinase in endothelial cells. In order to avoid the produc tion and screening of multiple transgenic lines we used embryonic stem cell and embryoid body technology to identify recombinant embryonic stem cell c lones with high, endothelial-specific Cre activity. One embryonic stem cell clone that showed high Cre activity in endothelial cells was used to gener ate germline chimeras. The in vivo efficiency and specificity of the transg enic Cre was analysed by intercrossing the tie-1-Cre line with the ROSA26R reporter mice. At initial stages of vascular formation (E8-9), LacZ stainin g was detected in almost all cells of the forming vasculature, Between E10 and birth, LacZ activity was detected in most endothelial cells within the embryo and of extra-embryonic tissues such as yolk sac and chorioallantoic placenta. Ectopic expression of Cre was observed in approximately 12-20% of the adult erythroid, myeloid and lymphoid cells and in subregions of the a dult brain. These results show that the tie-1-Cre transgenic strain can eff iciently direct deletion of floxed genes in endothelial cells in vivo.