R-Spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea

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DOIResolve DOI: http://doi.org/10.1038/ncomms2816
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TypeArticle
Journal titleNature Communications
ISSN2041-1723
Volume4
Article number1898
Subjectalpha smooth muscle actin; beta actin; beta catenin; cyclin D1; matrilysin; messenger RNA; Myc protein; protein; spondin 2; unclassified drug; Wnt protein; coliform bacterium; diarrheal disease; homeostasis; infectious disease; ion; molecular analysis; pathogen; physiological response; rodent; signal; animal experiment; article; Citrobacter rodentium; colon mucosa; diarrhea; gene expression; gene locus; genetic susceptibility; infection sensitivity; ion transport; mouse; nonhuman; signal transduction; single nucleotide polymorphism
AbstractCitrobacter 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. © 2013 Macmillan Publishers Limited. All rights reserved.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Biotechnology Research Institute (BRI-IRB)
Peer reviewedYes
NPARC number21269962
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Record identifier19b9b7cd-0df0-485b-8bcd-880af9665472
Record created2013-12-13
Record modified2016-05-09
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