Ablation of the GNB3 gene in mice does not affect body weight, metabolism or blood pressure, but causes bradycardia

作者：Ye Yuanchao; Sun Zhizeng; Guo Ang; Song Long sheng; Grobe Justin L; Chen Songhai^*

来源：Cellular Signalling, 2014, 26(11): 2514-2520.

DOI：10.1016/j.cellsig.2014.07.030

• Heterotrimeric G protein
• GNB3
• GPCR
• Polymorphism
• Blood pressure
• Metabolism

G protein beta 3 (G beta 3) is an isoform of heterotrimeric G protein beta subunits involved in transducing G protein coupled receptor (GPCR) signaling. Polymorphisms in G beta 3 (GNB3) are associated with many human disorders (e.g. hypertension, diabetes and obesity) but the role of GNB3 in these pathogeneses remains unclear. Here, G beta 3-null mice (GNB3(-/-)) were characterized to determine how G beta 3 functions to regulate blood pressure, body weight and metabolism. We found G beta 3 expression restricted to limited types of tissues, including the retina, several regions of the brain and heart ventricles. G beta 3-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, G beta 3-null mice had slower heart rates (similar to 450 vs similar to 500 beats/min). This bradycardia was not observed in isolated and perfused G beta 3-null mouse hearts. Moreover, mouse hearts isolated from GNB3(-/-) and controls responded equivalently to muscarinic receptor- and beta-adrenergic receptor-stimulated bradycardia and tachycardia, respectively. Since no difference was seen in isolated hearts, G beta 3 is unlikely to be involved directly in the GPCR signaling activity that controls heart pacemaker activity. These results demonstrate that although GP appears dispensable in mice for the regulation of blood pressure, body weight and metabolic features associated with obesity and diabetes, G beta 3 may regulate heart rate.

• 出版日期2014-11