title: Remodeling the mammalian heart using transgenesis.
abstract: Our objective was to test the hypothesis that, via transgenesis, one can modify the contractile protein complement of the mouse heart. Using a promoter derived from the mouse myosin heavy chain gene (alpha-MyHC), we attempted to remodel the mouse myocardium by ectopically expressing a ventricular form of the myosin light chain 2 (MLC2v) in the atrium. The ability of the heart to maintain contractile isoform stoichiometry was tested by overexpressing the cDNA in both the atria and ventricle. The promoter drove high levels of transgene expression in both cardiac compartments and was controlled in an appropriate manner during development. The data show that ectopic overexpression of a contractile protein isoform can lead to compartment specific replacement. However, if the transgene encodes the isoform that is normally present (e.g., MLC2v expressed in the ventricle), the protein levels remain unaffected, although the transgenic transcript accumulates to very high levels. The basic function and the physiologic or pathophysiologic significance of differential MLC2 isoform content was examined. Using the whole working heart preparation, we show that an MLC2a --> MLC2v shift in the atrium severely affects contractile function and performance.
authors.affiliation: Division of Molecular Cardiovascular Biology, Children's Hospital Research Foundation, Cincinnati, OH 45267, USA.
authors.forename: J
authors.initials: J
authors.lastname: Palermo
authors.forename: J
authors.initials: J
authors.lastname: Gulick
authors.forename: W
authors.initials: W
authors.lastname: Ng
authors.forename: I L
authors.initials: IL
authors.lastname: Grupp
authors.forename: G
authors.initials: G
authors.lastname: Grupp
authors.forename: J
authors.initials: J
authors.lastname: Robbins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000235:genetics* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D018076:DNA, Complementary; D018994:Myosin Light Chains