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
James B. Duke Professor of Medicine
The focus of work in this laboratory is on the elucidation of the molecular properties
and regulatory mechanisms controlling the function of G protein-coupled receptors.
As model systems we utilize the so called adrenergic receptors for adrenaline and
related molecules. The goal is to learn the general principles of signal transduction
from the outside to the inside of the cell which are involved in systems as diverse
as sensory perception, neuro- transmitter and hormonal signaling. Stud
Carmelo Alessio Milano
Professor of Surgery
Howard Allan Rockman
Edward S. Orgain 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
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