Tie2-Cre Transgenic Mice: A New Model for Endothelial Cell-Lineage Analysis in Vivo

• Published in: Developmental biology 2001-02, Vol.230 (2), p.230-242
• Main Authors: Kisanuki, Yaz Y, Hammer, Robert E, Miyazaki, Jun-ichi, Williams, S.Clay, Richardson, James A, Yanagisawa, Masashi
• Format: Article
• Language: English
• Subjects: Animals; atrioventricular canal; beta-Galactosidase - analysis; beta-Galactosidase - genetics; cardiac outflow tract; Cre-loxP; Embryonic and Fetal Development; endocardial cushion; Endocardium - embryology; Endothelium, Vascular - embryology; Enhancer Elements, Genetic; Gene Expression Regulation, Developmental; Heart - embryology; Integrases - genetics; Integrases - metabolism; Mice; Mice, Transgenic; Models, Animal; Promoter Regions, Genetic; Receptor Protein-Tyrosine Kinases - genetics; Receptor, TIE-2; Reverse Transcriptase Polymerase Chain Reaction; Viral Proteins
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1006/dbio.2000.0106

Endocardial cells are thought to contribute at least in part to the formation of the endocardial cushion mesenchyme. Here, we created Tie2-Cre transgenic mice, in which expression of Cre recombinase is driven by an endothelial-specific promoter/enhancer. To analyze the lineage of Cre expressing cells, we used CAG-CAT-Z transgenic mice, in which expression of lacZ is activated only after Cre-mediated recombination. We detected pan-endothelial expression of the Cre transgene in Tie2-Cre;CAG-CAT-Z double-transgenic mice. This expression pattern is almost identical to Tie2-lacZ transgenic mice. However, interestingly, we observed strong and uniform lacZ expression in mesenchymal cells of the atrioventricular canal of Tie2-Cre;CAG-CAT-Z double-transgenic mice. We also detected lacZ expression in the mesenchymal cells in part of the proximal cardiac outflow tract, but not in the mesenchymal cells of the distal outflow tract and branchial arch arteries. LacZ staining in Tie2-Cre;CAG-CAT-Z embryos is consistent with endocardial–mesenchymal transformation in the atrioventricular canal and outflow tract regions. Our observations 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 cardiac neural crest. Tie2-Cre transgenic mice are a new genetic tool for the analyses of endothelial cell-lineage and endothelial cell–specific gene targeting.