Tissue‐specific and inducible Cre‐mediated recombination in the gut epithelium

TLDR

The study generated two complementary Cre‑mediated recombination systems for the mouse digestive epithelium and tested them with a Cre‑reporter strain. Cre was expressed under a 9 kb villin regulatory region (vil‑Cre) and a tamoxifen‑dependent vil‑Cre‑ER T2 was also created for spatiotemporal somatic recombination. Recombination began at E9 in visceral endoderm and by E12.5 throughout the intestinal epithelium, persisted into adulthood, was inducible across the digestive tract with tamoxifen, remained detectable for 60 days post‑treatment, and thus targets epithelial progenitors, making these mice valuable tools for lineage and gene function studies. © 2004 Wiley‑Liss, Inc.; genesis 39:186–193, 2004.

Abstract

Abstract 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‐ER T2 ) 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‐ER T2 mice provide valuable tools for studies of cell lineage allocation and gene function in the developing and adult intestine. genesis 39:186–193, 2004. © 2004 Wiley‐Liss, Inc.