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The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
An antibiotic-responsive mouse model of fulminant ulcerative colitis
Silvia S Kang1, Seth M Bloom, Lyse A Norian
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Plos Medicine
|March 6, 2008
Summary
Multiple genetic defects in immune regulation created a novel mouse model of severe ulcerative colitis. This model, showing sensitivity to antibiotics and anti-cytokine therapy, advances IBD research.
Area of Science:
- Immunology
- Gastroenterology
- Genetics
Background:
- Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, presents a wide spectrum of pathology severity.
- Current mouse models often use single genetic defects, failing to replicate severe human IBD or distinguish between ulcerative colitis and Crohn's disease.
- A lack of severe IBD models hinders research into disease mechanisms and therapeutic development.
Purpose of the Study:
- To test the hypothesis that multiple genetic hits in intestinal immune regulation can create severe, reproducible IBD models.
- To develop a novel mouse model that mimics human ulcerative colitis or Crohn's disease pathology.
Main Methods:
- Generated a novel mouse line (dnKO) with combined defects in TGFbetaRII and IL-10R2 signaling.
- Observed disease development, pathogenesis, and response to therapeutic interventions.
Main Results:
- The dnKO mice rapidly developed a severe, fulminant ulcerative colitis-like disease, distinct from single-defect models.
- Pathogenesis involved uncontrolled proinflammatory cytokine production, largely due to T cell activation.
- Disease severity was reduced by anti-IFNgamma and anti-TNFalpha antibodies and completely inhibited by broad-spectrum antibiotics.
Conclusions:
- Developed the first mouse model of fulminant ulcerative colitis by combining multiple genetic immune regulatory defects.
- The model demonstrates sensitivity to anticytokine therapy and broad-spectrum antibiotics, suggesting potential therapeutic applications.
- The IL-10 and TGFbeta pathways synergize to suppress microbially induced proinflammatory cytokines, highlighting their role in ulcerative colitis pathogenesis.
