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 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.
Milano
C A
CA
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
Dolber
P C
PC
Rockman
H A
HA
Bond
R A
RA
Venable
M E
ME
Allen
L F
LF
Lefkowitz
R J
RJ
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis; D001794:Blood Pressure; D001835:Body Weight; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004075:Diglycerides / Q000378:metabolism; D015870:Gene Expression; D006352:Heart Ventricles; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009218:Myosins / Q000235:genetics; D009929:Organ Size; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000502:physiology*; D012016:Reference Values; D010738:Type C Phospholipases / Q000378:metabolism
D004075:Diglycerides; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D009320:Atrial Natriuretic Factor; D010738:Type C Phospholipases; D009218:Myosins