These ET+ transgenic mice express the human endothelin (EDN1 or ET-1) gene and a β-galactosidase (lacZ) reporter, both regulated by the bidirectional tetracycline operator, tetO. Homozygous mice are viable, fertile, and normal in size. ET-1 is a vasoconstrictor expressed in endothelial cells, and is a key mediator in vascular tone and renal homeostatsis. When mated to a mutant strain expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA), LacZ and ET-1 expression may be regulated with the tetracycline analog doxycycline (DOX) in the double mutant offspring.
When bred to a strain expressing tTA driven by α-myosin heavy chain (α-MHC) cardiomyocyte specific (see Stock No. 003170) overexpression of lacZ and ET-1 results in left ventricular dilation, contractile dysfunction, cardiac enlargement, and widespread inflammation upon removal of DOX. These mice exhibit decreased activity, hunched posture, and labored breathing, resulting in death within days of onset. These mice may be useful as for studying congestive heart failure, and idiopathic dilated cardiomyopathy (DCM).
When bred to a strain expressing tTA in cardiac tissue (Tg(Myh6-tTA)6Smbf, see Stock No. 017770 for example), this mutant mouse strain may be useful in studies of endothelin 1 and inflammation and dilated cardiomyopathy.
