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Transfer of naive T cells into the severe combined immunodeficiency (SCID) or recombination activating gene 2 (Rag2) deficient mouse models is a highly reproducible and easily manipulated model of colitis that has characteristics similar to chronic, idiopathic inflammatory bowel disease (IBD) in humans. Female Fox Chase C.B-17 SCID or Rag2 -/- mice, which lack B and T cells, are inoculated intraperitoneally (IP) with CD45RBhigh CD4+ T cells from congenic donor mice to induce disease with morphological features resembling human ulcerative colitis (UC) or Crohn’s disease (CD)1. IBD induced in SCID or Rag mice by transfer of CD45RBhigh CD4+ T cells involves differential activation of TH1 cells, which emphasizes the importance of an intact immune system in regulating intestinal inflammation2. Intestinal microflora also play a role in the development of the disease; however the mechanisms by which microflora influence mucosal immune responses are unclear3. In this model, mice develop intestinal lesions extending diffusely from the cecum to the rectum, which are characterized by extensive leukocytic infiltrates, epithelial cell hyperplasia with glandular elongation, ulceration, and loss of mucin-secreting goblet cells. Clinical symptoms include progressive weight loss and loose, mucous stool1. This model may be useful for studying mucosal immunoregulation as it relates to the pathogenesis of IBD. Immune manipulations that inhibit TH1 cell activation, such as anti-IFN-g monoclonal antibody treatment or systemic administration of recombinant IL-10, have been shown to be of significant benefit in this model1.

Optional Endpoint

  • PK/PD blood collections
  • Cytokine/chemokine analysis via Luminex(R)
  • Other sandwich ELISAs
  • CBC/clinical chemistry analysis
  • Soft tissue collection
  • Histopathologic analysis
  • Immunohistochemistry analysis
  • Endoscopy


  1. Read S, and Powrie F. Induction of Inflammatory Bowel Disease in Immunodeficient Mice by Depletion of Regulatory T Cells. Curr Protoc Immunol. 1999;30 suppl:15.13.1–15.13.10.
  2. Leach, Michael W., Andrew G. D. Bean, et al. Inflammatory Bowel Disease in C.B-17 SCID Mice Reconstituted with the CD45RBhigh Subset of CD4+ T Cells. Am J Pathol. 1996;148(5):1503–1515.
  3. Boismenu R, and Chen Y. Insights from mouse models of colitis. J Leukoc Biol. 2000;67(3):267–278.

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