Myocardial deletion of Smad4 using a novel α skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract
2010
Mohamad Azhar, Pei-Yu Wang, Tony Frugier, Kyoko Koishi, Chuxia Deng, Peter G. Noakes, Ian S. McLennan
<p>SMAD4 acts as the converging point for TGFβ and BMP signaling in heart development. Here, we investigated the role of SMAD4 in heart development using a novel α skeletal muscle actin Cre recombinase (<i>MuCre</i>) transgenic mouse strain. Lineage tracing using <i>MuCre</i>/<i>ROSA26<sup>LacZ</sup></i> reporter mice indicated strong Cre-recombinase expression in developing and adult heart and skeletal muscles. In heart development, significant <i>MuCre</i> expression was noted at E11.5 in the atrial, ventricular, outflow tract and atrioventricular canal myocardium, but not in the endocardial cushions. <i>MuCre</i>-driven conditional deletion of <i>Smad4</i> in mice caused double outlet right ventricle (DORV), ventricular septal defect (VSD), impaired trabeculation and thinning of ventricular myocardium, and mid-gestational embryonic lethality. In conclusion, <i>MuCre</i> mice effectively delete genes in both heart and skeletal muscles, thus enabling the discovery that myocardial <i>Smad4</i> deletion causes misalignment of the outflow tract and DORV.</p>
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