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Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy.

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Date
1994-10-11
Authors
Milano, CA
Dolber, PC
Rockman, HA
Bond, RA
Venable, ME
Allen, LF
Lefkowitz, RJ
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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 article
Subject
Animals
Atrial 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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https://hdl.handle.net/10161/7840
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Scholars@Duke

Lefkowitz

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
Milano

Carmelo Alessio Milano

Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery
Rockman

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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