Open AccessMyocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy.
Author(s) -
Carmelo A. Milano,
Paul C. Dolber,
Howard A. Rockman,
Richard A. Bond,
Mark E. Venable,
Lee F. Allen,
Robert J. Lefkowitz
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.21.10109
Subject(s) - transgene , genetically modified mouse , endocrinology , medicine , biology , muscle hypertrophy , cardiac myocyte , receptor , alpha (finance) , diacylglycerol kinase , myocyte , signal transduction , microbiology and biotechnology , gene , biochemistry , protein kinase c , construct validity , nursing , patient satisfaction
Transgenic mice were generated by using the alpha-myosin heavy chain promoter coupled to the coding sequence of a constitutively active mutant alpha 1B-adrenergic receptor (AR). These transgenic animals demonstrated cardiac-specific expression of this alpha 1-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.