Spontaneous Chronic Colitis in TCRα-Mutant Mice; an Experimental Model of Human Ulcerative Colitis

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Abstract
Mice with targeted disruption of the T cell receptor α gene (TCRα-/-) 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 TCRα-/- mice. Cytokines, specifically IL-4 and IL-1, also play an important role in the development of colitis in TCRα-/- mice. Enteric bacteria located in the large intestine are an important factor in the pathogenesis of this colitis because germ-free TCRα-/- mice do not develop colitis and appendectomy at an early age delays the onset of this colitis. The colitis in TCRα-/- mice resembles human ulcerative colitis and provides a useful model to study the pathogenesis of human inflammatory bowel disease.