title: 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 alpha -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 were unchanged. In contrast, ventricular expression of the transgene had no effect at the protein level, despite an eightfold increase in MLC2v transcript levels. The data show that sarcomeric protein stoichiometry is maintained rigorously via posttransciptional regulation and that protein replacement can be achieved through a single transgenic manipulation.
authors.affiliation: Children's Hospital Research Foundation, Cincinnati, Ohio, USA.
authors.forename: J
authors.initials: J
authors.lastname: Palermo
authors.forename: J
authors.initials: J
authors.lastname: Gulick
authors.forename: M
authors.initials: M
authors.lastname: Colbert
authors.forename: J
authors.initials: J
authors.lastname: Fewell
authors.forename: J
authors.initials: J
authors.lastname: Robbins
mesh_terms: D000818:Animals; D001483:Base Sequence; D006321:Heart / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*; D019076:Transgenes