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

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.