Tie2-Cre transgenic mice: A new model for endothelial cell-lineage analysis in vivo

Endocardial cells are thought to contribute at least in part to the formati on of the endocardial cushion mesenchyme. Here, we created Tie2-Cre transge nic mice, in which expression of Cre recombinase is driven by an endothelia l-specific promoter/enhancer. To analyze the lineage of Cre expressing cell s, we used CAG-CAT-Z transgenic mice, in which expression of lacZ is activa ted only after Cre-mediated recombination. We detected pan-endothelial expr ession of the Cre transgene in Tie2-Cre;CAG-CAT-Z double-transgenic mice. T his expression pattern is almost identical to Tie2-lacZ transgenic mice. Ho wever, interestingly, we observed strong and uniform lacZ expression in mes enchymal cells of the atrioventricular canal of Tie2-Cre;CAG-CAT-Z double-t ransgenic mice. We also detected lacZ expression in the mesenchymal cells i n part of the proximal cardiac outflow tract, but not in the mesenchymal ce lls of the distal outflow tract and branchial arch arteries. LacZ staining in Tie2-Cre;CAG-CAT-Z embryos is consistent with endocardial-mesenchymal tr ansformation in the atrioventricular canal and outflow tract regions. Our o bservations are consistent with previously reported results from Cx43-lacZ, Wnt1-Cre;R26R, and Pax3-Cre;R26R transgenic mice, in which lacZ expression in the cardiac outflow tract identified contributions in part from the car diac neural crest. Tie2-Cre transgenic mice are a new genetic tool for the analyses of endothelial cell-lineage and endothelial cell-specific gene tar geting. (C) 2001 Academic Press.