Generation of Smad7(-Cre) recombinase mice: A useful tool for the study of epithelial-mesenchymal transformation within the embryonic heart.

Smad7 can be induced by various transforming growth factor-beta superfamily ligands and negatively modulates their signaling, thus acting in a negative, autocrine feedback manner. Previous analyses have demonstrated that although Smad7 is widely expressed, it is predominantly found in the vascular endothelium. Because of the restricted spatiotemporal reporter expression driven via a novel 4.3 kb Smad7 promoter in endocardial cells overlying the hearts atrioventricular (AV) cushions; we hypothesized that a transgenic Cre line would prove useful for the analysis of endocardial cushion and valve formation. Here we describe a mouse line, Smad7(Cre), where Cre is robustly expressed within both cardiac outflow and AV endocardial cushions. Additionally, as endocardial cells are thought to contribute at least in part to the formation of the endocardial cushion mesenchyme, we crossed the Smad7(Cre) mice to the ROSA26(eGFP-DTA) diphtheria toxin A-expressing mice in order to genetically ablate Smad7(Cre) expressing cells. Ablation of Smad7(Cre) cells resulted in embryonic lethality by E11.5 and largely acellular endocardial cushions. 2009 Wiley-Liss, Inc.