Spontaneous chronic colitis in TCR alpha-mutant mice; an experimental model of human ulcerative colitis

Int Rev Immunol. 2000;19(1):123-38. doi: 10.3109/08830180009048393.


Mice with targeted disruption of the T cell receptor alpha gene (TCR alpha-/-) spontaneously develop chronic colitis. Colonic inflammation begins at 6-8 weeks of age and chronic colitis is established in about 60% of mice by 16-20 weeks of age. The disease is also associated with autoantibodies (anti-tropomyosin antibodies, anti-neutrophil cytoplasmic antibodies) and an oligoclonal immune response to luminal bacterial antigens. Although T cells, but not B cells or autoantibodies, are essential for the development of colitis, B cells and/or autoantibodies may have a regulatory role in the pathogenesis of this colitis because the colitis is more severe in B cell deficient TCR alpha-/- mice. Cytokines, specifically IL-4 and IL-1, also play an important role in the development of colitis in TCR alpha-/- mice. Enteric bacteria located in the large intestine are an important factor in the pathogenesis of this colitis because germ-free TCR alpha-/- mice do not develop colitis and appendectomy at an early age delays the onset of this colitis. The colitis in TCR alpha-/- mice resembles human ulcerative colitis and provides a useful model to study the pathogenesis of human inflammatory bowel disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Chronic Disease
  • Colitis, Ulcerative / immunology*
  • Colitis, Ulcerative / microbiology
  • Colitis, Ulcerative / pathology
  • Cytokines / immunology
  • Disease Models, Animal*
  • Humans
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • T-Lymphocytes / immunology


  • Cytokines
  • Receptors, Antigen, T-Cell, alpha-beta