Background: Animal models are an important tool to understand intestinal biology. Our laboratory previously generated C57BL/6-Tg(Car1-cre)5Flt transgenic mice (CAC) with large-intestine-specific Cre recombinase (Cre) expression as a model to study colon health.
Aim: To expand the utility of the CAC mouse model by determining the impact of chemically induced colitis on CAC transgene expression.
Methods: CAC mice were crossed to Rosa reporter mice (Rosa26R (flox/flox) ) with a lox-STOP-lox signal controlling β-galactosidase (βgal) expression and then further crossed with Apc(CKO/CKO) mice in some experiments to delete Apc alleles (Apc (Δ580) ). Initially, 8-week-old CAC(Tg/WT);Rosa26R (flox/WT) ;Apc (Δ580/WT) mice were treated with dextran sulfate sodium (DSS) in drinking water (5 days, 0, 0.65, 1.35, or 2.0 %). Colon tissue damage and βgal labeling were analyzed 10 day after stopping DSS. Next, 8-week-old CAC(Tg/WT);Rosa26R(flox/flox) mice were treated with 0 or 1.35 % DSS, and colonic βgal labeling was assessed at 30 day post-DSS treatment. Finally, 10-week-old CAC(Tg/WT);Apc (Δ580/WT) mice were treated with DSS (0 or 2 %) for 5 days and colonic tumors were analyzed at 20 weeks.
Results: CAC(Tg/WT);Rosa26R (flox/WT) ;Apc (Δ580/WT) mice had a DSS dose-dependent increase in colon epithelial damage that correlated with increased epithelial βgal labeling at 10 days (r (2) = 0.9, β = 0.75). The βgal labeling in CAC(Tg/WT);Rosa26R(flox/flox) mice colon remained high at 30 days, especially in the crypts of the healed ulcer. DSS also increased colon tumor incidence and multiplicity in CAC(Tg/WT);Apc (Δ580/WT) mice.
Conclusions: DSS-mediated epithelial damage induces a persistent, Cre-mediated recombination of floxed alleles in CAC mice. This enables the examination of gene function in colon epithelium during experimental colitis and colitis-induced colon cancer.
Keywords: Colitis; Colorectal cancer; Cre recombinase; Transgenic animal model.