Tissue-specific and inducible Cre-mediated recombination in the gut epithelium.
We generated two complementary systems for Cre-mediated recombination of target genes in the mouse digestive epithelium and tested them with a Cre-reporter mouse strain. Cre was expressed under the control of a 9 kb regulatory region of the murine villin gene (vil-Cre). Genetic recombination was initiated at embryonic day (E) 9 in the visceral endoderm, and by E12.5 in the entire intestinal epithelium, but not in other tissues. Cre expression was maintained throughout adulthood. Furthermore, transgenic mice bearing a tamoxifen-dependent Cre recombinase (vil-Cre-ERT2) expressed under the control of the villin promoter were created to perform targeted spatiotemporally controlled somatic recombination. After tamoxifen treatment, recombination was detectable throughout the digestive epithelium. The recombined locus persisted for 60 days after tamoxifen administration, despite rapid intestinal cell renewal, indicating that epithelial progenitor cells had been targeted. The villin-Cre and villin-Cre-ERT2 mice provide valuable tools for studies of cell lineage allocation and gene function in the developing and adult intestine.
el Marjou
Fatima
F
Morphogenesis and intracellular signalling, Institut Curie-CNRS, Paris, France.
Janssen
Klaus-Peter
KP
Chang
Benny Hung-Junn
BH
Li
Mei
M
Hindie
Valérie
V
Chan
Lawrence
L
Louvard
Daniel
D
Chambon
Pierre
P
Metzger
Daniel
D
Robine
Sylvie
S
D000818:Animals; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D018390:Gene Targeting / Q000379:methods*; D015151:Immunoblotting; D019426:Integrases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011995:Recombination, Genetic / Q000187:drug effects / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology; D019076:Transgenes / Q000235:genetics; D001616:beta-Galactosidase
D017931:DNA Primers; D008024:Ligands; D008840:Microfilament Proteins; C026615:villin; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase