Pan-myocardial expression of Cre recombinase throughout mouse development

Mouse-lines expressing Cre recombinase in a tissue-specific manner are a powerful tool in developmental biology. Here, we report that a 3 kb fragment of the Xenopus laevis myosin light-chain 2 (XMLC2) promoter drives Cre recombinase expression in a cardiac-restricted fashion in the mouse embryo. We have isolated two XMLC2-Cre lines that express recombinase exclusively within cardiomyocytes, from the onset of their differentiation in the cardiac crescent of the early embryo. Expression is maintained throughout the myocardium of the embryonic heart tube and subsequently the mature myocardium of the chambered heart. Recombinase activity is detected in all myocardial tissue, including the pulmonary veins. One XMLC2-Cre line shows uniform expression while the other only expresses recombinase in a mosaic fashion encompassing less than 50% of the myocardial cells. Both lines cause severe cardiac malformations when crossed to a conditional Tbx5 line, resulting in embryonic death at midgestation. Optical projection tomography reveals that the spectrum of developmental abnormalities includes a shortening of the outflow tract and its abnormal alignment, along with a dramatic reduction in trabeculation of the ventricular segment of the looping heart tube.