Heritable susceptibility for colitis in mice induced by IL‐10 deficiency

Severity of inflammatory bowel disease in IL‐10 gene‐targeted mice is in part determined by genetic background. In the current study, a targeted IL‐10 gene was transferred into the C3H/HeJBir substrain, known to exhibit high T‐cell and B‐cell responses to enteric flora, and to be highly sensitive to colitigenic stress. IL‐10‐deficient C3H/HeJBir mice developed early onset colitis in contrast to IL‐10‐deficient C57BL/6J congenic mice. Histopathologic analysis of disease in C3H/HeJBir. Il10–/– and C57BL/6J. Il10–/– mice showed significant differences at all ages studied. Hybrids of these congenic strains (F1. Il10–/–) were produced to study the mode of inheritance as well as subphenotypes that correlated with histopathology. Lesions in F1 mice were intermediate between parental strains. C3H‐contributed subphenotypes that correlated best with histopathology were peripheral blood granulocyte percentage, serum amyloid A concentration, spleen weight/body weight ratio, and mesenteric lymph node weight/body weight ratio. Neither enhanced humoral immunity (secretory IgA, anti‐Escherichia coli cellular membrane Ig) characteristic of C3H/HeJBir, nor T‐cell percentages in peripheral blood correlated as well. This study represents a necessary step in elucidating murine genetic modifiers controlling colitis sensitivity.