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 pre- and postnatal development. Current efforts are primarily directed towards increasing the efficiency of this recombination system in mice. We have generated transgenic mouse lines expressing a tamoxifen-activated Cre recombinase, CreER(T2), under the control of the smooth muscle-specific SM22 promoter. Both a randomly integrated transgene [SM-CreER(T2)(tg)] and a transgene 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(T2)(tg) mice compared with SM-CreER(T2)(ki) mice. Whereas no recombinase activity could be detected in vehicle-treated SM-CreER(T2)(ki) mice, administration of tamoxifen induced the excision of a loxP-flanked reporter transgene in up to 100% of smooth muscle cells. The recombined genome persisted for at least four months after tamoxifen treatment. SM-CreER(T2)(ki) transgenic mice should be useful to study the effects of various somatic mutations in smooth muscle.
Kühbandner
S
S
Institut für Pharmakologie und Toxikologie, Technische Universität München, München, Germany.
Brummer
S
S
Metzger
D
D
Chambon
P
P
Hofmann
F
F
Feil
R
R
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018390:Gene Targeting; D007274:Injections, Intraperitoneal; D019426:Integrases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D009124:Muscle Proteins / Q000235:genetics; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D016254:Mutagenesis, Insertional / Q000187:drug effects / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology; D011995:Recombination, Genetic / Q000187:drug effects; D013629:Tamoxifen / Q000008:administration & dosage; D019076:Transgenes / Q000187:drug effects / Q000502:physiology; D014764:Viral Proteins
D008840:Microfilament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C058992:Tagln protein, mouse; D014764:Viral Proteins; C051615:transgelin; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases