Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Murine models of ulcerative colitis


Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology limited to the large intestine. The disease is prevalent in industrial societies and is associated with specific ethnic populations. A number of murine models, each focused on distinct aspects of the disease process, were developed over the past 20 years to further our understanding of the pathogenesis of UC. These models have been and remain our best resource for the study of the disorder as a result of their homology to human UC and the ease in which they can be manipulated and examined. This review examines and distills what has been learned from these models and how this information is related back to human UC.

This is a preview of subscription content, log in to check access.


  1. Autenrieth, I. B., Bucheler, N., Bohn, E., Heinze, G., and Horak, I., Cytokine mRNA expression in intestinal tissue of inter-leukin-2 deficient mice with bowel inflammation.Gut, 41, 793–800 (1997).

  2. Brandwein, S. L., McCabe, R. P., Cong, Y., Waites, K. B., Ridwan, B. U., Dean, P. A., Ohkusa, T., Birkenmeier, E. H., Sundberg, J. P., and Elson, C. O., Spontaneously colitic C3H/HeJBir mice demonstrate selective antibody reactivity to antigens of the enteric bacterial flora.J. Immunol., 159, 44–52 (1997).

  3. Burich, A., Hershberg, R., Waggie, K., Zeng, W., Brabb, T., Westrich, G., Viney, J. L., and Maggio-Price, L.,Helicobacter-induced inflammatory bowel disease in IL-10 and T cell deficient mice.Am. J. Physiol., 281, G764–778 (2001).

  4. Cong, Y., Brandwein, S. L., McCabe, R. P., Lazenby, A., Birkenmeier, E. H., Sundberg, J. P., and Elson, C. O., CD4+ T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: Increased T helper cell type 1 response and ability to transfer disease.J. Exp. Med., 187, 855–864 (1998).

  5. Croop, J. M., Raymond, M., Haber, D., Devault, A., Arceci, R. J., Gros, P., and Housman, D. E., The three mouse multidrug resistance (mdr) genes are expressed in a tissue specific manner in normal mouse tissue.Mol. Cell. Biol., 9, 1346–1350 (1989).

  6. Desvignes, C., Bour, H., Nicolas, J. F., and Kaiserlain, D., Lack of oral tolerance but oral priming for contact sensitivity to dinitrofluorobenzene in major histocompatibility complex class II-deficient mice and in CD4(+) T cell-depleted mice.Eur. J. Imm., 26, 1756–1761, (1996).

  7. Ehrhardt, R. O., Ludviksson, B. R., Gray, B., Neurath, M., and Strober, W., Induction and prevention of colonic inflammation in IL-2-deficient mice.J. Immunol., 158, 566–573 (1997).

  8. Elson, C. O., Cong, Y., and Sundberg J., The C3H/HeBir mouse model: a high susceptibility phenotype for colitis.Int. Rev. Immunol., 19, 63–75 (2000).

  9. Gillen, C. D., Walmsley, R. S., Prior, P., Andrews, H. A., and Allan, R. N., Ulcerative colitis and Crohn’s disease: A comparison of the colorectal cancer risk in extensive colitis.Gut, 35, 1590–1592 (1994).

  10. Grusby, M. J., Johnson, R. S., Papaioannou, V. E., and Glimcher, L. H., Depletion of CD4+ T cells in major histocompatability complex class II deficient mice.Science, 253, 1417–1420 (1991).

  11. Gupta, S. K., Gallego, C., Johnson, G. L., and Heasley, L. E., MAP kinase is constitutively activated ingip2 andsrc transformed rat 1a fibroblasts.J. Biol. Chem., 267, 7987–7990 (1992).

  12. Hermiston, M. L. and Gordon, J. I., Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin.Science, 270, 1203–1207 (1995).

  13. Hiatt, R. A. and Kaufman, L., Epidemiology of inflammatory bowel disease in a defined northern California population.West. J. Med., 149, 541–546 (1988).

  14. Homquist, C. E., Lu, X., Rogers-Fani, P. M., Rudolph, U., Shappell, S., Birnbaumer, L., and Harriman, G. R., Gβi2-deficient mice with colitis exhibit a local increase in memory CD4+ T cells and proinflammatory Th1-type cytokines.J. Immunol., 158, 1068–1077 (1997).

  15. Jaffee, B. D., Manos, E. J., Collins, R. J., Czerniak, P. M., Favata, M. F., Magolda, R. L., Scherle, P. A., and Trzaskos, J. M., Inhibition of MAP kinase kinase (MEK) results in an anti-inflammatory responsein vivo.Biochem. Biophys. R. Comm., 268, 647–651 (2000).

  16. Ma, A., Datta, M., Margosian, E., Chen, J., and Horak, I., T cells, but not B cells, are required for bowel inflammation in interleukin 2-deficient mice.J. Exp. Med., 182, 1567–1572 (1995).

  17. Maggio-Price, L., Shows, D., Waggie, K., Burich, A., Zeng, W., Escobar, S., Morrissey, P., and Viney, J. L.,Helicobacter bilis infection accelerates andH. hepaticus infections delays the development of colitis in multiple drug resistance deficient (mdrla’) mice.Am. J. Path., 160, 739–751 (2002).

  18. Mahler, M., Bristol, I. J., Leiter, E. H., Workman, A. E., Birkenmeier, E. H., Elson, C. O., and Sundberg, J. P., Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis.Am. J. Physiol., 274, G544-G551 (1998).

  19. McDonald, S. A. C., Palmen, M. J. H. J., Van Rees, E. P., and MacDonald, T. T., Characterization of the mucosal cell mediated immune response in IL-2 knockout mice before and after the onset of colitis.Immunology, 91, 73–80 (1997).

  20. Mizoguchi, A., Mizoguchi, E., Chiba, C., Spiekermann, G. M., Tonegawa, S., Nagler-Anderson, C., and Bhan, A. K., Cytokine imbalance and autoantibody production in T cell receptor-αmutant mice with inflammatory bowel disease.J. Exp. Med., 183, 847–856 (1996).

  21. Mombaerts, P., Clarke, A. R., Hooper, M. L., and Tonewaga, S., Creation of a large genomic deletion at the T-cell antigen receptor β-subunit locus in mouse embryonic stem cells by gene targeting.Proc. Natl. Acad. Sci. USA, 88, 3084–3087 (1991).

  22. Mombaerts, P., Clarke, A. R., Rudnicki, M. A., lacomini, J., Itohara, S., LaFaille, J. J., Wang, L., Ichikawa, Y., Jaenisch, R., Hooper, M. L., and Tonegawa, S., Mutations in T-cell antigen receptor genes α and β block thymocyte development at different stages.Nature, 360, 225–231 (1992).

  23. Mombaerts, P., Mizoguchi, E., Grusby, M. J., Glimcher, L. H., Bhan, A. K., and Tonegawa, S., Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice.Cell, 75, 275–282 (1993).

  24. Ohman, L., Franzen, L., Rudolph, U., Harriman, G. R., and Homquist, E. H., Immune activation in the intestinal mucosa before the onset of colitis in Gαi2-deficient mice.Scand. J. Immunol., 52, 80–90 (2000).

  25. Panwala, C. M., Jones, J. C., and Viney, J. L., A novel model of inflammatory bowel disease: Mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis.J. Immunol., 161, 5733–5744 (1998).

  26. Rudolph, U., Finegold, M. J., Rich, S. S., Harriman, G. R., Srinivasan, Y., Brabet, P., Boulay, G., Bradley, A., and Birnbaumer, L., Ulcerative colitis and adenocarcinoma of the colon in Gαi2-deficinet mice.Nat. Gen., 10, 143–150 (1995a).

  27. Rudolph, U., Finegold, M. J., Rich, S. S., Harriman, G. R., Srinivasan, Y., Brabet, P., Bradley, A., and Bimbaumer, L., Gi2a protein deficiency: A model for inflammatory bowel disease.J. Clin. Immunol., 15, 101S-105S (1995b).

  28. Sadlack, B., Merz, H., Schorle, H., Schimpl, A., Feller, A. C., and Horak, I., Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene.Cell, 75, 253–261 (1993).

  29. Schinkel, A. H., Smit, J. J. M., van Tellingen, O., Beijnen, J. H., Wagenaar, E., van Deemter, L., Mol, C. A. A. M., van der Valk, M. A., Robanus-Maandag, E. C., te Riele, H. P. J., Berns, A. J. M., and Borst, P., Disruption of the mouse mdrla P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs.Cell, 77, 491–502 (1994).

  30. Schorle, H., Holtschkle, T., Hunig, T., Schimpl, A., and Horak, I., Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting.Nature, 352, 621–624 (1991)

  31. Schultz, M., Tonkonogy, S. L., Sellon, R. K., Veltkamp, C., Godfrey, V. L., Kwon, J., Grenther, W. B., Balish, E., Horak, I., and Sartor, R. B., IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation.Am. J. Physiol., 276, G1461-G1472 (1999).

  32. Shah, S. A., Simpson, S. J., Brown, L. F., Comiskey, M., de Jong, Y. P., Allen, D., and Terhorst, C., Development of colonic adenocarcinomas in a mouse model of ulcerative colitis-associated colon cancer.Gastroenterology, 120, A447 (2001)

  33. Simpson, S. J., Mizoguchi, E., Allen, D., Bhan, A. K., and Terhost, C., Evidence that CD4+, but not CD8+ T cells are responsible for murine interieukin-2-deficient colitis.Eur. J. Immunol., 25, 2618–2625 (1995).

  34. Snider, D. P., Liang, H., Switzer, I., and Underdown, B. J., IgA production in MHC class II-deficient mice is primarily a function of B-1 a cells.Inter. Imm., 11, 191–198 (1999).

  35. Sohn, K., Shah, S. A., Reid, S., Choi, M., Carrier, J., Comiskey, M., Terhorst, C., and Kim, Y., Molecular genetics of ulcerative colitis-associated colon cancer in the interleukin 2- and β2-microglobulin-deficient mouse.Cancer Res., 61, 6912–6917 (2001)

  36. Stowe, S. P., Redmond, S. R., Stormont, J. M., Shah, A. N., Chessin, L. N., Segal, H. L., and Chey, W. Y., An epidemiologic study of inflammatory bowel disease in Rochester, New York.Gastroenterology, 98, 104–110 (1990).

  37. Sundberg, J. P., Elson, C. O., Bedgian, H., and Birkenmeier, H., Spontaneous heritable colitis in a new substrain of C3H/HeJ mice.Gastroenterology, 107, 1726–1735 (1994)

  38. Takashi, I., Kiyono, H., and Hamada, S., CD4+ T-cell population mediates development of inflammatory bowel disease in T-cell receptor α chain deficient mice.Gastroenterology, 112, 1876–1886 (1997)

  39. Thiebaut, F., Tsuruo, T., Hamada, H., Bgottesman, M. M., Pastan, I., and Willingham, M. C., Cellular localizaton of the multidrug resistance gene product in normal human tissues.Proc. Natl. Acad. Sci. USA, 84, 7735–7738 (1987).

  40. Uhlig, H. H., Hornquist, E. H., Bache, L. O., Rudolph, U., Bimbaumer, L., and Mothes, T., Antibody response to dietary and autoantigens in Gαi2-deficient mice.Eur. J. Gastro. Hepato., 13, 1421–1429 (2001).

  41. Waidmann, M., Allemand, Y., Lehmann, J., Genaro, S. D., Bucheler, N., Hamann, A., and Autenrieth, I. B., Microflora reactive IL-10 producing regulatory T cells are present in the colon of IL-2 deficient mice but lack efficacious inhibition of IFN-γand TNF-β production.Gut, 50, 170–179 (2002).

Download references

Author information

Correspondence to Christopher Flynn or Joel Levine or Daniel W. Rosenberg.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Flynn, C., Levine, J. & Rosenberg, D.W. Murine models of ulcerative colitis. Arch Pharm Res 26, 433–440 (2003). https://doi.org/10.1007/BF02976857

Download citation

Key words

  • Ulcerative colitis
  • Murine models
  • Colon
  • Cancer
  • Inflammation