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Updated: May 11, 2026

Investigating Intestinal Inflammation in DSS-induced Model of IBD
Published on: February 1, 2012
R-spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea
Olivier Papapietro1, Sarah Teatero, Ajitha Thanabalasuriar
1Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4.
Abstract:
Citrobacter rodentium is a natural mouse pathogen widely used as a model for enteropathogenic and enterohemorrhagic Escherichia coli infections in humans. While C. rodentium causes self-limiting colitis in most inbred mouse strains, it induces fatal diarrhoea in susceptible strains. The physiological pathways as well as the genetic determinants leading to susceptibility have remained largely uncharacterized. Here we use a forward genetic approach to identify the R-spondin2 gene as a major determinant of susceptibility to C. rodentium infection. Robust induction of R-spondin2 expression during infection in susceptible mouse strains causes a potent Wnt-mediated proliferative response of colonic crypt cells, leading to the generation of an immature and poorly differentiated colonic epithelium with deficiencies in ion-transport components. Our data demonstrate a previously unknown role of R-spondins and Wnt signalling in susceptibility to infectious diarrhoea and identify R-spondin2 as a key molecular link between infection and intestinal homoeostasis.
Insights
R-spondin2 gene identified as key to susceptibility in Citrobacter rodentium infection. Its induction causes Wnt-driven proliferation, leading to immature colons and severe diarrhea in mice.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Citrobacter rodentium is a mouse model for human E. coli infections.
- Susceptibility to C. rodentium infection is linked to genetic factors and physiological pathways.
- Understanding these determinants is crucial for infectious diarrhea research.
Purpose of the Study:
- To identify genetic determinants of susceptibility to Citrobacter rodentium infection.
- To elucidate the role of Wnt signaling in infectious colitis.
Main Methods:
- Forward genetic screen in mice.
- Analysis of gene expression during infection.
- Assessment of colonic epithelium differentiation and function.
Main Results:
- R-spondin2 gene identified as a major determinant of susceptibility.
- Infection induces R-spondin2 expression in susceptible mice.
- R-spondin2 drives Wnt-mediated crypt cell proliferation, resulting in immature colonic epithelium.
Conclusions:
- R-spondin2 and Wnt signaling play a critical role in susceptibility to infectious diarrhea.
- R-spondin2 is a key molecular link between infection and intestinal homeostasis.
- This study uncovers a novel mechanism of host-pathogen interaction.
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