title: Ablation of the GNB3 gene in mice does not affect body weight, metabolism or blood pressure, but causes bradycardia.
abstract: G protein β3 (Gβ3) is an isoform of heterotrimeric G protein β subunits involved in transducing G protein coupled receptor (GPCR) signaling. Polymorphisms in Gβ3 (GNB3) are associated with many human disorders (e.g. hypertension, diabetes and obesity) but the role of GNB3 in these pathogeneses remains unclear. Here, Gβ3-null mice (GNB3(-/-)) were characterized to determine how Gβ3 functions to regulate blood pressure, body weight and metabolism. We found Gβ3 expression restricted to limited types of tissues, including the retina, several regions of the brain and heart ventricles. Gβ3-deficient mice were normal as judged by body weight gain by age or by feeding with high-fat diet (HFD); glucose tolerance and insulin sensitivity; baseline blood pressure and angiotensin II infusion-induced hypertension. During tail-cuff blood pressure measurements, however, Gβ3-null mice had slower heart rates (~450 vs ~500 beats/min). This bradycardia was not observed in isolated and perfused Gβ3-null mouse hearts. Moreover, mouse hearts isolated from GNB3(-/-) and controls responded equivalently to muscarinic receptor- and β-adrenergic receptor-stimulated bradycardia and tachycardia, respectively. Since no difference was seen in isolated hearts, Gβ3 is unlikely to be involved directly in the GPCR signaling activity that controls heart pacemaker activity. These results demonstrate that although Gβ3 appears dispensable in mice for the regulation of blood pressure, body weight and metabolic features associated with obesity and diabetes, Gβ3 may regulate heart rate.
authors.affiliation: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Zhizeng
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Ang
authors.initials: A
authors.lastname: Guo
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Long-Sheng
authors.initials: LS
authors.lastname: Song
authors.affiliation: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Grobe
authors.affiliation: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: songhai-chen@uiowa.edu.
authors.forename: Songhai
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D001919:Bradycardia / Q000235:genetics / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism
chemical_list: C454420:G-protein beta3 subunit; D043562:Receptors, G-Protein-Coupled; D020962:Heterotrimeric GTP-Binding Proteins
keywords: Blood pressure; GNB3; GPCR; Heterotrimeric G protein; Metabolism; Polymorphism
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