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

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 phosphol...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-10, Vol.91 (21), p.10109-10113
Main Authors: Milano, C A, Dolber, P C, Rockman, H A, Bond, R A, Venable, M E, Allen, L F, Lefkowitz, R J
Format: Article
Language:English
Subjects:
Animals
Atrial Natriuretic Factor - biosynthesis
Blood Pressure
Body Weight
Cardiomegaly - genetics
Cardiomegaly - pathology
Cardiomegaly - physiopathology
Diglycerides - metabolism
Gene Expression
Heart Ventricles
Humans
Mice
Mice, Transgenic
Mutagenesis, Site-Directed
Myocardium - metabolism
Myocardium - pathology
Myosins - genetics
Organ Size
Point Mutation
Promoter Regions, Genetic
Radioligand Assay
Receptors, Adrenergic, alpha-1 - biosynthesis
Receptors, Adrenergic, alpha-1 - physiology
Reference Values
RNA, Messenger - analysis
RNA, Messenger - metabolism
Type C Phospholipases - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.21.10109