title: An Inducible, Large-Intestine-Specific Transgenic Mouse Model for Colitis and Colitis-Induced Colon Cancer Research.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Nutrition Science, Purdue University, 700 West State St., West Lafayette, IN, 47907-2059, USA.
authors.forename: Fa
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, 47907, USA.|Eli Lilly and Company, Lilly Corporate Center, 355 East Merrill St., Indianapolis, IN, 46225, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Johnson
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, 47907, USA.|Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, 47907, USA.|EPL, Inc., 45600 Terminal Dr. # 100, Sterling, VA, 20166, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Snyder
authors.affiliation: Purdue University Interdisciplinary Life Sciences Ph.D. Training Program, Purdue University, West Lafayette, IN, 47907, USA.|Department of Dermatology, Indiana University School of Medicine, 550 N. University Blvd., Suite 3240, Indianapolis, IN, 46202, USA.
authors.forename: Marsha L
authors.initials: ML
authors.lastname: DeSmet
authors.affiliation: Department of Nutrition Science, Purdue University, 700 West State St., West Lafayette, IN, 47907-2059, USA. fleet@purdue.edu.|Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, 47907, USA. fleet@purdue.edu.
authors.forename: James C
authors.identifier: http://orcid.org/0000-0002-0142-9517
authors.initials: JC
authors.lastname: Fleet
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D019426:Integrases; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011995:Recombination, Genetic; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D016264:Dextran Sulfate; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase
keywords: Colitis; Colorectal cancer; Cre recombinase; Transgenic animal model