Functions of the Wilms' tumor suppressor gene (Wt1) in embryonic and adult myocardium

Abstract

The Wilms’ tumor suppressor gene (Wt1) is expressed in several cell types in the developing and adult heart, including epicardial and endothelial cells, fibroblasts and cardiomyocytes. Systemic Wt1 deletion causes the death of the embryos at midgestation, and it also induces lethality when the systemic deletion is performed in adult mice. Wt1 expression in the embryonic epicardium is essential for the correct cardiac development, but little is known about its myocardial expression in embryonic and adult heart in homeostatic and pathological conditions, using a cardiotoxic drug. To study the roles that WT1 is playing in embryonic and adult cardiomyocytes, we evaluated the consequences of its conditional deletion in two transgenic mouse models, and then analysed the histological and molecular effects of its ablation. In addition, we also analysed possible changes in the morphology and function of adult mice carrying the embryonic Wt1 deletion. To evaluate the consequences of Wt1 deletion in the adult myocardium under pathological conditions, we administered an acute and a chronic treatment of doxorubicin. Our results suggested that the myocardial Wt1 expression is essential for the correct heart development and its presence is key in adult cardiomyocytes, especially in pathological conditions.