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

Ian J. Bristol, Mark A. Farmer, Yingzi Cong, Xin Xiao Zheng, Terry B. Strom, Charles O. Elson, John P. Sundberg, Edward H. Leiter

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Severity of inflammatory bowel disease in IL-10 gene-targeted mice is in part determined by genetic back-ground. 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 his-topathology. 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.

Original languageEnglish (US)
Pages (from-to)290-302
Number of pages13
JournalInflammatory bowel diseases
Volume6
Issue number4
DOIs
StatePublished - 2000

Keywords

  • Colitis
  • Genetics
  • Interleukin 10
  • Mice
  • Pathology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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  • Cite this

    Bristol, I. J., Farmer, M. A., Cong, Y., Zheng, X. X., Strom, T. B., Elson, C. O., Sundberg, J. P., & Leiter, E. H. (2000). Heritable susceptibility for colitis in mice induced by IL-10 deficiency. Inflammatory bowel diseases, 6(4), 290-302. https://doi.org/10.1097/00054725-200011000-00006