Determinants of the cardiomyopathic phenotype in chimeric mice overexpressing cardiac Gsα

Dorothy E. Vatner, Gui Ping Yang, Yong Jian Geng, Kuniya Asai, Jeung S. Yun, Thomas E. Wagner, Yoshihiro Ishikawa, Sanford P. Bishop, Charles J. Homcy, Stephen F. Vatner

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Mice with overexpressed cardiac Gsα develop cardiomyopathy, characterized by myocyte hypertrophy and extensive myocardial fibrosis. The cardiomyopathy likely involves chronically enhanced β-adrenergic signaling, because it can be blocked with long-term propranolol treatment. It remains unknown whether the genotype of the myocyte is solely responsible for the progressive pathological changes. A chimeric population in the heart should answer this question. Accordingly, we developed a chimeric animal, which combined cells from a transgenic overexpressed Gsα parent and a Rosa mouse containing the LacZ reporter gene, facilitating identification of the non- Gsα cells, which express a blue color with exposure to β-galactosidase. We studied these animals at 14 to 17 months of age (when cardiomyopathy should have been present), with the proportion of Gsα cells in the myocardium ranging from 5% to 88%. β-Galactosidase staining of the hearts demonstrated Gsα and Rosa cells, exhibiting a mosaic pattern. The fibrosis and hypertrophy, characteristic of the cardiomyopathy, were not distributed randomly. There was a direct correlation (r=0.85) between the extent of myocyte hypertrophy (determined by computer imaging) and the quantity of Gsα cells. The fibrosis, determined by picric acid Sirius red, was also more prominent in areas with the greatest Gsα cell density, with a correlation of r=0.88. Thus, the overexpressed Gsα can exert its action over the life of the animal, resulting in a local picture of cardiomyopathic damage in discrete regions of the heart, where clusters of the overexpressed Gsα cells reside, sparing the clusters of normal cells derived from the normal Rosa parent.

Original languageEnglish (US)
Pages (from-to)802-806
Number of pages5
JournalCirculation Research
Volume86
Issue number7
DOIs
StatePublished - Apr 14 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology

Keywords

  • Cardiomyopathy
  • Heart failure β-adrenergic receptor
  • Hypertrophy
  • Sympathetic nervous system

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