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R-spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea.

Olivier Papapietro | Sarah Teatero | Ajitha Thanabalasuriar | Kyoko E Yuki | Eduardo Diez | Lei Zhu | Eugene Kang | Sandeep Dhillon | Aleixo M Muise | Yves Durocher | Martin M Marcinkiewicz | Danielle Malo | Samantha Gruenheid
Nature communications | 2013

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.

Pubmed ID: 23695692

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: Canadian Institutes of Health Research, Canada
    Id: 15461-4
  • Agency: Canadian Institutes of Health Research, Canada
    Id: 89817-1
  • Agency: CIHR, Canada
    Id: MOP-89817

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AxioVision Imaging System (tool)

RRID:SCR_002677

Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376

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Mouse Genome Informatics (MGI) (tool)

RRID:SCR_006460

International database for laboratory mouse. Data offered by The Jackson Laboratory includes information on integrated genetic, genomic, and biological data. MGI creates and maintains integrated representation of mouse genetic, genomic, expression, and phenotype data and develops reference data set and consensus data views, synthesizes comparative genomic data between mouse and other mammals, maintains set of links and collaborations with other bioinformatics resources, develops and supports analysis and data submission tools, and provides technical support for database users. Projects contributing to this resource are: Mouse Genome Database (MGD) Project, Gene Expression Database (GXD) Project, Mouse Tumor Biology (MTB) Database Project, Gene Ontology (GO) Project at MGI, and MouseCyc Project at MGI.

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FVB/NJ (tool)

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Mus musculus with name FVB/NJ from IMSR.

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RRID:IMSR_JAX:000664

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AKR/J (tool)

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Mus musculus with name AKR/J from IMSR.

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C3H/HeOuJ (tool)

RRID:IMSR_JAX:000635

Mus musculus with name C3H/HeOuJ from IMSR.

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