Temporally controlled somatic mutagenesis in smooth muscle

Genesis. 2000 Sep;28(1):15-22. doi: 10.1002/1526-968x(200009)28:1<15::aid-gene20>3.0.co;2-c.


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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Gene Targeting
  • Injections, Intraperitoneal
  • Integrases / biosynthesis
  • Integrases / genetics*
  • Integrases / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins*
  • Muscle Proteins / genetics
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Mutagenesis, Insertional / drug effects
  • Mutagenesis, Insertional / genetics*
  • Organ Specificity / genetics
  • Promoter Regions, Genetic / physiology
  • RNA, Messenger / biosynthesis
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / physiology
  • Recombination, Genetic* / drug effects
  • Tamoxifen / administration & dosage
  • Transgenes / drug effects
  • Transgenes / physiology
  • Viral Proteins*


  • Microfilament Proteins
  • Muscle Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Tagln protein, mouse
  • Viral Proteins
  • transgelin
  • Tamoxifen
  • Cre recombinase
  • Integrases