Temporally controlled somatic mutagenesis in smooth muscle

Ligand-dependent site-specific recombinases are powerful tools to engineer the mouse genome in specific somatic cell types at selected times during pr e- and postnatal development. Current efforts are primarily directed toward s increasing the efficiency of this recombination system in mice. We have g enerated transgenic mouse lines expressing a tamoxifen-activated Cre recomb inase, CreER(T2), under the control of the smooth muscle-specific SM22 prom oter. Both a randomly integrated transgene [SM-CreER(T2)(tg)] and a transge ne that has been "knocked in" into the endogenous SM22 locus [SM-CreER(T2)( ki)] were expressed in smooth muscle-containing tissues. The level of CreER (T2) expression and tamoxifen-induced recombination was lower in SM-CreER(T 2)(tg) mice compared with SM-CreER(T2)(ki) mice. Whereas no recombinase act ivity could be detected in vehicle-treated SM-CreER(T2)(ki) mice, administr ation of tamoxifen induced the excision of a loxP-flanked reporter transgen e in up to 100% of smooth muscle cells. The recombined genome persisted for at least four months after tamoxifen treatment. SM-CreER(T2)(ki) transgeni c mice should be useful to study the effects of various somatic mutations i n smooth muscle. (C) 2000 Wiley-Liss, Inc.