Up-regulation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice

A cardiac homeobox-containing gene Csx/Nkx2-5, which is essential for cardi ac development, is abundantly expressed in the adult heart as well as in th e heart primordia. Targeted disruption of this gene results in embryonic le thality due to abnormal heart morphogenesis. To elucidate the role of Csx/N bx2-5 in the adult heart, we generated transgenic mice which overexpress hu man Csx/Nkx2-5. The transgene was expressed abundantly in the heart and the skeletal muscle. mBNA levels of several cardiac genes including nartriuret ic peptides, CARP, MLC2 upsilon, and endogenous Csx/Nkx2-5 were increased i n the ventricle of the transgenic mice. Electron microscopic analysis revea led that the ventricular myocardium of the transgenic mice had many secreto ry granules, which disappeared after administration of vasopressin. These r esults suggest that Csx/Nkx2-5 regulates many cardiac genes and induces for mation of secretory granulesinthe adult ventricle. (C) 2000 Academic Press.