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Updated: Jul 15, 2026
The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Citrobacter rodentium infection causes iNOS-independent intestinal epithelial dysfunction in mice
Andrew C Skinn1, Nathalie Vergnolle, Stella R Zamuner
1Mucosal Inflammation Research Group and Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr NW, Calgary, AB T2N 4N1, Canada.
Abstract:
Attaching-effacing bacteria are major causes of infectious diarrhea in humans worldwide. Citrobacter rodentium is an attaching-effacing enteric pathogen that causes transmissible murine colonic mucosal hyperplasia. We characterized colonic inflammation and ion transport at 3, 7, 10, 30, and 60 d after infection of C57Bl/6 mice with C. rodentium. Macroscopic damage score was significantly increased 7 and 10 d after infection. Colonic wall thickness was increased at 7, 10, 30, and 60 d. Myeloperoxidase (MPO) activity was significantly increased at 3, 7, and 10 d and returned to control levels by days 30 and 60. The expressions of inducible nitric oxide synthase and cyclooxygenase-2 were increased by C. rodentium infection. Significant reductions in the epithelial secretory response to carbachol, but not to electrical field stimulation or forskolin, were observed at 3 and 10 d of infection. Translocation of enteric bacteria into the mesenteric lymph nodes was observed 10 d following infection. There was no difference in response to infection between animals deficient in inducible nitric oxide synthase and wild-type controls. The COX-2 inhibitor rofecoxib caused decreased wall thickness and MPO activity at day 10. However, COX-2 inhibition did not alter infection-induced changes in ion transport. Citrobacter rodentium infection causes colonic inflammation, mucosal hyperplasia, and nitric-oxide-independent epithelial dysfunction in association with increased permeability to luminal bacteria.
Insights
Citrobacter rodentium infection causes significant colonic inflammation and hyperplasia in mice. This pathogen leads to nitric-oxide-independent epithelial dysfunction and increased gut permeability.
Area of Science:
- Microbiology
- Gastroenterology
- Immunology
Background:
- Attaching-effacing bacteria, like Citrobacter rodentium, are significant global causes of infectious diarrhea.
- C. rodentium serves as a model pathogen for studying transmissible murine colonic mucosal hyperplasia.
Purpose of the Study:
- To characterize colonic inflammation and ion transport dynamics following C. rodentium infection in mice.
- To investigate the roles of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the host response to infection.
Main Methods:
- Mice were infected with C. rodentium, and colonic tissues were analyzed at multiple time points (3, 7, 10, 30, 60 days).
- Macroscopic damage, colonic wall thickness, myeloperoxidase (MPO) activity, and gene expression (iNOS, COX-2) were assessed.
- Ion transport responses to various stimuli were measured, and bacterial translocation was evaluated.
- Experiments included comparisons between wild-type mice, iNOS-deficient mice, and treatment with a COX-2 inhibitor (rofecoxib).
Main Results:
- C. rodentium infection led to increased macroscopic damage, colonic wall thickness, and MPO activity, particularly at early time points (3-10 days).
- iNOS and COX-2 expression increased post-infection. Bacterial translocation to mesenteric lymph nodes occurred by day 10.
- Epithelial secretory responses to carbachol were reduced, but not to electrical field stimulation or forskolin, indicating specific ion transport dysfunction.
- iNOS deficiency did not alter the infection response, while COX-2 inhibition reduced inflammation markers but not ion transport changes.
Conclusions:
- Citrobacter rodentium infection induces colonic inflammation, mucosal hyperplasia, and epithelial dysfunction independent of nitric oxide.
- Increased intestinal permeability allows for bacterial translocation during infection.
- COX-2 plays a role in the inflammatory response but not in the observed epithelial ion transport defects.
