Ligand-Activated Site-Specific Recombination in Mice

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 l...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-10, Vol.93 (20), p.10887-10890
Main Authors: Feil, R., Brocard, J., Mascrez, B., LeMeur, M., Metzger, D., Chambon, P.
Format: Article
Language:English
Subjects:
Alleles
Animals
DNA
Gene Expression Regulation
Gene targeting
Genes
Genetic Engineering - methods
Genetic mutation
human cytomegalovirus
Integrases - chemistry
Integrases - metabolism
Ligands
Messenger RNA
Mice
Mice, Transgenic
Polymerase chain reaction
Receptors, Estrogen - chemistry
Receptors, Estrogen - metabolism
Recombinant Fusion Proteins - metabolism
Recombination, Genetic
Sequence Deletion
Tamoxifen - pharmacology
Transgenes
Transgenes - genetics
Transgenic animals
Viral Proteins
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Summary: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-ER$^{\text{T}}$, which is activated by tamoxifen, but not by estradiol. Transgenic mice were generated expressing Cre-ER$^{\text{T}}$ 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.20.10887