Transgenic Remodeling of the Contractile Apparatus in the Mammalian Heart

Abstract The structure-function relationships of the sarcomeric proteins in the mammalian cardiac compartment remain ill-defined because of the lack of a suitable model in which they can be readily manipulated or exchanged in vivo. To establish the validity of the transgenic paradigm for remodeling the mammalian heart, the murine α-cardiac myosin heavy chain gene promoter was used to express a ventricular myosin light chain-2 transgene (MLC2v) in both the atria and ventricles of the adult animal. Expression resulted in high levels of the transgene’s transcript in both compartments. In the ventricle, the transgene was expressed against the background expression of the normal isoform. In the atrium, the transgene’s expression would be ectopic, in that normally, MLC2v expression is restricted to the ventricle. Ectopic expression of the transgene in the atria resulted in a complete replacement of the atrial myosin light chain-2 protein isoform, although the endogenous isoform’s steady state transcript levels ...