Chemically Induced Mouse Models of Colitis

Maximilian J. Waldner1, Markus F. Neurath1

1 Department of Medicine, University of Erlangen, Erlangen, Germany
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.55
DOI:  10.1002/0471141755.ph0555s46
Online Posting Date:  September, 2009
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

Crohn's disease (CD) and ulcerative colitis (UC), both of which are referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders of the gastrointestinal tract that have characteristic clinical, pathological, endoscopic, and radiologic features. Knowledge about the pathogenesis of IBD has dramatically increased in recent years based in part on the use of experimental models of IBD. Although none of these models exactly mimics the human disorder, they have proven to be useful for studying many important aspects of these conditions. Detailed in this unit is a description of the most commonly used chemically induced mouse models of IBD. These include trinitrobenzene sulfonic acid (TNBS), oxazolone, and acute or chronic dextran sodium sulfate (DSS) colitis models. Curr. Protoc. Pharmacol. 46:5.55.1‐5.55.15. © 2009 by John Wiley & Sons, Inc.

Keywords: inflammatory bowel disease; colitis; disease models; animal; mice; dextran sulfate; trinitrobenzenesulfonic acid

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Trinitrobenzene Sulfonic Acid (TNBS)–Induced Colitis
  • Basic Protocol 2: Oxazolone‐Induced Colitis
  • Basic Protocol 3: Acute Dextran Sulfate Sodium (DSS)–Induced Colitis
  • Alternate Protocol 1: Chronic Dextran Sulfate Sodium (DSS)–Induced Colitis
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: Trinitrobenzene Sulfonic Acid (TNBS)–Induced Colitis

  Materials
  • 6‐ to 12‐week‐old mice
  • 1% TNBS presensitization solution (see recipe)
  • Ketamine/xylazine solution (see recipe)
  • TNBS solution (see recipe)
  • Sterile phosphate‐buffered saline, calcium‐ and magnesium‐free (CMF‐PBS; Biochrom AG, cat. no. L182‐10)
  • 3‐mm dermal ear punch (Fine Science Tools, cat. no. 24210‐02)
  • Balance (accurate to 0.1 g)
  • Electric razor
  • 1‐ml syringe
  • 3.5 French (F) catheter (1.2‐mm in diameter) or a blunt‐tip steel gavage needle; mark this catheter at 4‐cm length beginning from the tip
  • Sterile forceps and scissors
  • Additional reagents and equipment for cervical dislocation of the mouse (Donovan and Brown, )

Basic Protocol 2: Oxazolone‐Induced Colitis

  Materials
  • 6‐ to 12‐week‐old mice
  • 3% oxazolone presensitization solution (see recipe)
  • Ketamine/xylazine solution (see recipe)
  • 1% oxazolone solution (see recipe)
  • Sterile phosphate‐buffered saline, calcium‐ and magnesium‐free (CMF‐PBS; Biochrom AG, cat. no. L182‐10)
  • Electric razor
  • 3‐mm dermal ear punch (Fine Science Tools, cat. no. 24210‐02)
  • Balance (accurate to 0.1 g)
  • 1‐ml syringe
  • 3.5‐French (F) catheter (1.2‐mm in diameter) or a blunt‐tip steel gavage needle; mark this catheter at 4‐cm length beginning from the tip)
  • Sterile forceps and scissors
  • Additional reagents and equipment for cervical dislocation of the mouse (Donovan and Brown, )

Basic Protocol 3: Acute Dextran Sulfate Sodium (DSS)–Induced Colitis

  Materials
  • 6‐ to 12‐week‐old mice
  • 2% DSS solution (see recipe)
  • Autoclaved drinking water
  • Sterile phosphate‐buffered saline, calcium‐ and magnesium‐free (CMF‐PBS; Biochrom AG, cat. no. L182‐10)
  • Balance (accurate to 0.1 g)
  • 3 mm dermal ear punch (Fine Science Tools, cat. no. 24210‐02)
  • Sterile forceps and scissors
  • Additional reagents and equipment for cervical dislocation of the mouse (Donovan and Brown, )
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
   Becker, C., Fantini, M.C., Wirtz, S., Nikolaev, A., Kiesslich, R., Lehr, H.A., Galle, P.R., and Neurath, M.F. 2005. In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy. Gut 54:950‐954.
   Becker, C., Dornhoff, H., Neufert, C., Fantini, M.C., Wirtz, S., Huebner, S., Nikolaev, A., Lehr, H.A., Murphy, A.J., Valenzuela, D.M., Yancopoulos, G.D., Galle, ,P.R., Karow, M., and Neurath, M.F. 2006. Cutting edge: IL‐23 cross‐regulates IL‐12 production in T cell‐dependent experimental colitis. J. Immunol. 177:2760‐2764.
   Boirivant, M., Fuss, I.J., Chu, A., and Strober, W. 1998. Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. J. Exp. Med. 188:1929‐1939.
   Dieleman, L.A., Ridwan, B.U., Tennyson, G.S., Beagley, K.W., Bucy, R.P., and Elson, C.O. 1994. Dextran sulfate sodium‐induced colitis occurs in severe combined immunodeficient mice. Gastroenterology 107:1643‐1652.
   Dieleman, L.A., Palmen, M.J., Akol, H., Bloemena, E., Peña, A.S., Meuwissen, S.G., and Van Rees, E.P. 1998. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin. Exp. Immunol. 114:385‐391.
   Donovan, J. and Brown, P. 2006. Euthanasia. Curr. Protoc. Immunol. 73:1.8.1‐1.8.4.
   Ekström, G.M. 1998. Oxazolone‐induced colitis in rats: effects of budesonide, cyclosporin A, and 5‐aminosalicylic acid. Scand. J. Gastroenterol. 33:174‐179.
   Fichtner‐Feigl, S., Fuss, I.J., Preiss, J.C., Strober, W., and Kitani, A. 2005. Treatment of murine Th1‐ and Th2‐mediated inflammatory bowel disease with NF‐kappa B decoy oligonucleotides. J. Clin. Invest. 115:3057‐3071.
   Heller, F., Fuss, I.J., Nieuwenhuis, E.E., Blumberg, R.S., and Strober, W. 2002. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL‐13‐producing NK‐T cells. Immunity 17:629‐638.
   Heller, F., Florian, P., Bojarski, C., Richter, J., Christ, M., Hillenbrand, B., Mankertz, J., Gitter, A.H., Bürgel, N., Fromm, M., Zeitz, M., Fuss, I., Strober, W., and Schulzke, J.D. 2005. Interleukin‐13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129:550‐564.
   Morris, G.P., Beck, P.L., Herridge, M.S., Depew, W.T., Szewczuk, M.R., and Wallace, J.L. 1989. Hapten‐induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795‐803.
   Mudter, J., Amoussina, L., Schenk, M., Yu, J., Brüstle, A., Weigmann, B., Atreya, R., Wirtz, S., Becker, C., Hoffman, A., Atreya, I., Bi esterfeld, S., Galle, P.R., Lehr, H.A., Rose‐John, S., Mueller, C., Lohoff, M., and Neurath, M. 2008. The transcription factor IFN regulatory factor‐4 controls experimental colitis in mice via T cell‐derived IL‐6. J. Clin. Invest. 118:2415‐2426.
   Murthy, S.N., Cooper, H.S., Shim, H., Shah, R.S., Ibrahim, S.A., and Sedergran, D.J. 1993. Treatment of dextran sulfate sodium‐induced murine colitis by intracolonic cyclosporin. Dig. Dis. Sci. 38:1722‐1734.
   Myers, K.J., Murthy, S., Flanigan, A., Witchell, D.R., Butler, M., Murray, S., Siwkowski, A., Goodfellow, D., Madsen, K., and Baker, B. 2003. Antisense oligonucleotide blockade of tumor necrosis factor‐alpha in two murine models of colitis. J. Pharmacol. Exp. Ther. 304:411‐424.
   Neurath, M.F., Fuss, I., Kelsall, B.L., Stüber, E., and Strober, W. 1995. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J. Exp. Med. 182:1281‐1290.
   Okayasu, I., Hatakeyama, S., Yamada, M., Ohkusa, T., Inagaki, Y., and Nakaya, R. 1990. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694‐702.
   Pantzar, N., Ekström, G.M., Wang, Q., and Weström, B.R. 1994. Mechanisms of increased intestinal [51Cr]EDTA absorption during experimental colitis in the rat. Dig. Dis. Sci. 39:2327‐2333.
   Sartor, R.B. 2006. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat. Clin. Pract. Gastroenterol. Hepatol. 3:390‐407.
   Shen, C., de Hertogh, G., Bullens, D.M., Van Assche, G., Geboes, K., Rutgeerts, P., and Ceuppens, J.L. 2007. Remission‐inducing effect of anti‐TNF monoclonal antibody in TNBS colitis: mechanisms beyond neutralization? Inflamm. Bowel Dis. 13:308‐316.
   Strober, W., Fuss, I.J., and Blumberg, R.S. 2002. The immunology of mucosal models of inflammation. Annu. Rev. Immunol. 20:495‐549.
   Wirtz, S. and Neurath, M.F. 2007. Mouse models of inflammatory bowel disease. Adv. Drug Deliv. Rev. 59:1073‐1083.
   Xavier, R.J. and Podolsky, D.K. 2007. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427‐434.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library