Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy.
Abstract
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.
Type
Journal articleSubject
AnimalsAtrial Natriuretic Factor
Blood Pressure
Body Weight
Cardiomegaly
Diglycerides
Gene Expression
Heart Ventricles
Humans
Mice
Mice, Transgenic
Mutagenesis, Site-Directed
Myocardium
Myosins
Organ Size
Point Mutation
Promoter Regions, Genetic
RNA, Messenger
Radioligand Assay
Receptors, Adrenergic, alpha-1
Reference Values
Type C Phospholipases
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Show full item recordScholars@Duke
Robert J. Lefkowitz
The Chancellor's Distinguished Professor of Medicine
Dr. Lefkowitz’s memoir, A Funny Thing Happened on the Way to Stockholm, recounts his
early career as a cardiologist and his transition to biochemistry, which led to his
Nobel Prize win.
Robert J. Lefkowitz, M.D. is James B. Duke Professor of Medicine and Professor of
Biochemistry and Chemistry at the Duke University Medical Center. He has been an Investigator
of the
Carmelo Alessio Milano
Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery
Howard Allan Rockman
Edward S. Orgain Distinguished Professor of Cardiology, in the School of Medicine
Rockman Lab: Molecular Mechanisms of Hypertrophy and Heart Failure Overall Research
Direction: The major focus of this laboratory is to understand the molecular mechanisms
of hypertrophy and heart failure. My laboratory uses a strategy that combines state
of the art molecular techniques to generate transgenic and gene targeted mouse models,
combined with sophisticated physiologic measures of in vivo cardiac function. In this
manner, candidate molecules are either selectively overexp
Alphabetical list of authors with Scholars@Duke profiles.
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