Journal article
Ablation of the GNB3 gene in mice does not affect body weight, metabolism or blood pressure, but causes bradycardia
Cellular signalling, Vol.26(11), pp.2514-2520
11/2014
DOI: 10.1016/j.cellsig.2014.07.030
PMCID: PMC4160384
PMID: 25093805
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 ~500beats/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.
•Gβ3 is expressed in restricted tissues•Ablation of Gβ3 in mice does not affect body weight, metabolisms, and blood pressure•Gβ3–null mice exhibit bradycardia
Details
- Title: Subtitle
- Ablation of the GNB3 gene in mice does not affect body weight, metabolism or blood pressure, but causes bradycardia
- Creators
- Yuanchao Ye - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAZhizeng Sun - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAAng Guo - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USALong-sheng Song - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAJustin L Grobe - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USASonghai Chen - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Cellular signalling, Vol.26(11), pp.2514-2520
- DOI
- 10.1016/j.cellsig.2014.07.030
- PMID
- 25093805
- PMCID
- PMC4160384
- NLM abbreviation
- Cell Signal
- ISSN
- 0898-6568
- eISSN
- 1873-3913
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/501100001677, name: National Institute of Health, award: GM094255
- Language
- English
- Date published
- 11/2014
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984040238402771
Metrics
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