Myocardial expression of a constitutively active α1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy

Carmelo A. Milano, Paul C. Dolber, Howard A. Rockman, Richard A. Bond, Mark E. Venable, Lee F. Allen, Robert J. Lefkowitz

Research output: Contribution to journalArticle

319 Citations (Scopus)

Abstract

Transgenic mice were generated by using the α-myosin heavy chain promoter coupled to the coding sequence of a constitutively active mutant α1B-adrenergic receptor (AR). These transgenic animals demonstrated cardiac-specific expression of this α1-AR with resultant activation of phospholipase C as shown by increased myocardial diacylglycerol content. A phenotype consistent with cardiac hypertrophy developed in adult transgenic mice with increased heart/body weight ratios, myocyte cross-sectional areas, and ventricular atrial natriuretic factor mRNA levels relative to nontransgenic controls. These transgenic animals may provide insight into the biochemical triggers that induce hypertrophy in cardiac disease and serve as a convenient experimental model for studies of this condition.

Original languageEnglish (US)
Pages (from-to)10109-10113
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number21
StatePublished - Oct 11 1994
Externally publishedYes

Fingerprint

Genetically Modified Animals
Cardiomegaly
Adrenergic Receptors
Transgenic Mice
Myosin Heavy Chains
Diglycerides
Atrial Natriuretic Factor
Type C Phospholipases
Muscle Cells
Hypertrophy
Heart Diseases
Theoretical Models
Body Weight
Phenotype
Messenger RNA

Keywords

  • Catecholamines
  • Phospholipase C

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Milano, C. A., Dolber, P. C., Rockman, H. A., Bond, R. A., Venable, M. E., Allen, L. F., & Lefkowitz, R. J. (1994). Myocardial expression of a constitutively active α1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America, 91(21), 10109-10113.

Myocardial expression of a constitutively active α1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. / Milano, Carmelo A.; Dolber, Paul C.; Rockman, Howard A.; Bond, Richard A.; Venable, Mark E.; Allen, Lee F.; Lefkowitz, Robert J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 21, 11.10.1994, p. 10109-10113.

Research output: Contribution to journalArticle

Milano, Carmelo A. ; Dolber, Paul C. ; Rockman, Howard A. ; Bond, Richard A. ; Venable, Mark E. ; Allen, Lee F. ; Lefkowitz, Robert J. / Myocardial expression of a constitutively active α1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 21. pp. 10109-10113.
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