© 1996 American Heart Association, Inc.
Articles |
Transgenic Remodeling of the Contractile Apparatus in the Mammalian Heart
From the Children's Hospital Research Foundation, Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio.
Correspondence to Dr Jeffrey Robbins, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, Cincinnati, OH 45229-3039. E-mail teachdna@aol.com.
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 
-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
posttranscriptional regulation and that protein replacement can be
achieved through a single transgenic manipulation.
Key Words: transgenic • myosin light chain • gene • muscle
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