Galvin-Parton P A, Chen X, Moxham C M, Malbon C C
Department of Pediatrics, Diabetes and Metabolic Diseases Research Program, University Medical Center, SUNY/Stony Brook, Stony Brook, New York 11794-8651, USA.
J Biol Chem. 1997 Feb 14;272(7):4335-41. doi: 10.1074/jbc.272.7.4335.
Transgenic BDF-1 mice harboring an inducible, tissue-specific transgene for RNA antisense to Galphaq provide a model in which to study a loss-of-function mutant of Galphaq in vivo. Galphaq deficiency induced in liver and white adipose tissue at birth produced increased body mass and hyperadiposity within 5 weeks of birth that persisted throughout adult life. Galphaq-deficient adipocytes display reduced lipolytic responses, shown to reflect a newly discovered, alpha1-adrenergic regulation of lipolysis. This alpha1-adrenergic response via phosphoinositide hydrolysis and activation of protein kinase C is lacking in the Galphaq loss-of-function mutants in vivo and provides a basis for the increased fat accumulation.
携带针对Gαq的RNA反义诱导型组织特异性转基因的转基因BDF-1小鼠提供了一个在体内研究Gαq功能丧失突变体的模型。出生时在肝脏和白色脂肪组织中诱导的Gαq缺乏在出生后5周内导致体重增加和肥胖，并持续至成年期。Gαq缺陷型脂肪细胞显示出脂解反应降低，这被证明反映了一种新发现的α1-肾上腺素能脂解调节。体内Gαq功能丧失突变体缺乏通过磷酸肌醇水解和蛋白激酶C激活的这种α1-肾上腺素能反应，这为脂肪积累增加提供了基础。
