Ligand-activated site-specific recombination in mice

Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10887-90. doi: 10.1073/pnas.93.20.10887.


Current mouse gene targeting technology is unable to introduce somatic mutations at a chosen time and/or in a given tissue. We report here that conditional site-specific recombination can be achieved in mice using a new version of the Cre/lox system. The Cre recombinase has been fused to a mutated ligand-binding domain of the human estrogen receptor (ER) resulting in a tamoxifen-dependent Cre recombinase, Cre-ERT, which is activated by tamoxifen, but not by estradiol. Transgenic mice were generated expressing Cre-ERT under the control of a cytomegalovirus promoter. We show that excision of a chromosomally integrated gene flanked by loxP sites can be induced by administration of tamoxifen to these transgenic mice, whereas no excision could be detected in untreated animals. This conditional site-specific recombination system should allow the analysis of knockout phenotypes that cannot be addressed by conventional gene targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Genetic Engineering / methods*
  • Integrases / chemistry*
  • Integrases / metabolism
  • Ligands
  • Mice
  • Mice, Transgenic
  • Receptors, Estrogen / chemistry*
  • Receptors, Estrogen / metabolism
  • Recombinant Fusion Proteins / metabolism*
  • Recombination, Genetic*
  • Sequence Deletion*
  • Tamoxifen / pharmacology*
  • Transgenes / genetics
  • Viral Proteins*


  • Ligands
  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Viral Proteins
  • Tamoxifen
  • Cre recombinase
  • Integrases