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Chemically induced mouse models of intestinal inflammation


Animal models of intestinal inflammation are indispensable for our understanding of the pathogenesis of Crohn disease and ulcerative colitis, the two major forms of inflammatory bowel disease in humans. Here, we provide protocols for establishing murine 2,4,6-trinitro benzene sulfonic acid (TNBS)-, oxazolone- and both acute and chronic dextran sodium sulfate (DSS) colitis, the most widely used chemically induced models of intestinal inflammation. In the former two models, colitis is induced by intrarectal administration of the covalently reactive reagents TNBS/oxazolone, which are believed to induce a T-cell-mediated response against hapten-modified autologous proteins/luminal antigens. In the DSS model, mice are subjected several days to drinking water supplemented with DSS, which seems to be directly toxic to colonic epithelial cells of the basal crypts. The procedures for the hapten models of colitis and acute DSS colitis can be accomplished in about 2 weeks but the protocol for chronic DSS colitis takes about 2 months.

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Figure 1: C57BL/6 mice were subjected to the TNBS or oxazolone colitis protocol as described in the text.
Figure 2: Acute DSS colitis C57BL/6 mice were subjected to the DSS colitis protocol as described in the text.


  1. Podolsky, D.K. Inflammatory bowel disease. N. Engl. J. Med. 347, 417–429 (2002).

    Article  CAS  Google Scholar 

  2. Wirtz, S. & Neurath, M.F. Animal models of intestinal inflammation: new insights into the molecular pathogenesis and immunotherapy of inflammatory bowel disease. Int. J. Colorectal Dis. 15, 144–160 (2000).

    Article  CAS  Google Scholar 

  3. Elson, C.O. et al. Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol. Rev. 206, 260–276 (2005).

    Article  Google Scholar 

  4. Neurath, M.F., Fuss, I., Kelsall, B.L., Stuber, E. & Strober, W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J. Exp. Med. 182, 1281–1290 (1995).

    Article  CAS  Google Scholar 

  5. Neurath, M.F., Pettersson, S., Meyer zum Buschenfelde, K.H. & Strober, W. Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Nat. Med. 2, 998–1004 (1996).

    Article  CAS  Google Scholar 

  6. Dohi, T. et al. Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses. J. Exp. Med. 189, 1169–1180 (1999).

    Article  CAS  Google Scholar 

  7. Ekstrom, G.M. Oxazolone-induced colitis in rats: effects of budesonide, cyclosporin A, and 5-aminosalicylic acid. Scand. J. Gastroenterol. 33, 174–179 (1998).

    Article  CAS  Google Scholar 

  8. Boirivant, M., Fuss, I.J., Chu, A. & Strober, W. Oxazolone colitis: a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. J. Exp. Med. 188, 1929–1939 (1998).

    Article  CAS  Google Scholar 

  9. Heller, F., Fuss, I.J., Nieuwenhuis, E.E., Blumberg, R.S. & Strober, W. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity 17, 629–638 (2002).

    Article  CAS  Google Scholar 

  10. Iijima, H. et al. Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1. J. Exp. Med. 199, 471–482 (2004).

    Article  CAS  Google Scholar 

  11. Okayasu, I. et al. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98, 694–702 (1990).

    Article  CAS  Google Scholar 

  12. Dieleman, L.A. et al. Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice. Gastroenterology 107, 1643–1652 (1994).

    Article  CAS  Google Scholar 

  13. Tanaka, T. et al. A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci. 94, 965–973 (2003).

    Article  CAS  Google Scholar 

  14. Mahler, M. et al. Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis. Am. J. Physiol. 274, G544–G551 (1998).

    CAS  PubMed  Google Scholar 

  15. Becker, C. et al. In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy. Gut 54, 950–954 (2005).

    Article  CAS  Google Scholar 

  16. Wirtz, S., Becker, C., Blumberg, R., Galle, P.R. & Neurath, M.F. Treatment of T cell-dependent experimental colitis in SCID mice by local administration of an adenovirus expressing IL-18 antisense mRNA. J. Immunol. 168, 411–420 (2002).

    Article  CAS  Google Scholar 

  17. Becker, C., Fantini, M.C. & Neurath, M.F. High resolution colonoscopy in live mice. Nat. Protocols 1, 2900–2907 (2006).

    Article  CAS  Google Scholar 

  18. Kojouharoff, G. et al. Neutralization of tumour necrosis factor (TNF) but not of IL-1 reduces inflammation in chronic dextran sulphate sodium-induced colitis in mice. Clin. Exp. Immunol. 107, 353–358 (1997).

    Article  CAS  Google Scholar 

  19. Rachmilewitz, D. et al. Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis. Gastroenterology 122, 1428–1441 (2002).

    Article  CAS  Google Scholar 

  20. Pfeiffer, C.J. & Qiu, B.S. Effects of chronic nitric oxide synthase inhibition on TNB-induced colitis in rats. J. Pharm. Pharmacol. 47, 827–832 (1995).

    Article  CAS  Google Scholar 

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Correspondence to Markus F Neurath.

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Wirtz, S., Neufert, C., Weigmann, B. et al. Chemically induced mouse models of intestinal inflammation. Nat Protoc 2, 541–546 (2007).

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