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Transgenic overexpression of cardiac actin in the mouse heart suggests coregulation of cardiac, skeletal and vascular actin expression

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Abstract

Previous studies have shown that depletion of cardiac actin by targeted disruption is associated with increased expression of alternative actins in the mouse heart. Here we have studied the effects of transgenic overexpression of cardiac actin using the α-myosin heavy chain promoter. Lines carrying 7 or 8 copies of the transgene showed a 2-fold increase in cardiac actin mRNA and also displayed decreased expression of skeletal and vascular actin in their hearts. In contrast, a line with more than 250 copies of the transgene did not show a similar decrease in the expression of skeletal and vascular actin despite a 3-fold increase in cardiac actin mRNA. While the low copy number transgenic mice displayed hearts that were similar to non-transgenic controls, the high copy number transgenic line showed larger hearts with distinct atrial enlargement and cardiomyocyte hypertrophy. Further, while the low copy number transgenic mouse hearts were mildly hypocontractile when compared with non-transgenic mouse hearts, the high copy number transgenic mouse hearts were significantly so. We conclude that in the presence of a small number of copies of the cardiac actin transgene, homeostatic mechanisms involved in maintaining actin levels are active and negatively regulate skeletal and vascular actin levels in the heart in response to increased expression of cardiac actin. However, these putative mechanisms are either inoperative in the high copy number transgenic line or are countered by the enhanced expression of skeletal and vascular actin during cardiomyocyte hypertrophy.

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Author notes

  1. R. Flick

    Present address: Molecular Ecology Research Branch, U.S. EPA, Cincinnati, OH, USA

Authors and Affiliations

  1. Division of Developmental Biology, University of Cincinnati, College of Medicine, Cincinnati, OH, 45229, USA

    A. Kumar, K. Crawford, R. Flick & J. L. Lessard

  2. Division of Molecular Cardiovascular Biology, University of Cincinnati, College of Medicine, Cincinnati, OH, 45229, USA

    R. Klevitsky & J. Robbins

  3. Division of Pathology, Childrens Hospital Medical Center, University of Cincinnati, College of Medicine, Cincinnati, OH, 45229, USA

    K. E. Bove

  4. Division of Molecular and Cellular Physiology, University of Cincinnati, College of Medicine, Cincinnati, OH, 45229, USA

    J. N. Lorenz

Authors
  1. A. Kumar
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  2. K. Crawford
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  3. R. Flick
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  4. R. Klevitsky
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  5. J. N. Lorenz
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  6. K. E. Bove
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  7. J. Robbins
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  8. J. L. Lessard
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Correspondence to A. Kumar.

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Kumar, A., Crawford, K., Flick, R. et al. Transgenic overexpression of cardiac actin in the mouse heart suggests coregulation of cardiac, skeletal and vascular actin expression. Transgenic Res 13, 531–540 (2004). https://doi.org/10.1007/s11248-004-2823-6

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  • DOI: https://doi.org/10.1007/s11248-004-2823-6

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