INDUCTION OF G-ALPHA(Q)-SPECIFIC ANTISENSE RNA IN-VIVO CAUSES INCREASED BODY-MASS AND HYPERADIPOSITY

Transgenic BDF-1 mice harboring an inducible, tissue-specific transgen e for RNA antisense to G alpha(q) provide a model in which to study a loss-of-function mutant of G alpha(q) in vivo. G alpha(q) deficiency i nduced in liver and white adipose tissue at birth produced increased b ody mass and hyperadiposity within 5 weeks of birth that persisted thr oughout adult life. G alpha(q)-deficient adipocytes display reduced li polytic responses, shown to reflect a newly discovered, alpha(1)-adren ergic regulation of lipolysis. This alpha(1)-adrenergic response via p hosphoinositide hydrolysis and activation of protein kinase C is lacki ng in the G alpha(q) loss-of-function mutants in vivo and provides a b asis for the increased fat accumulation.