Diarrhea as a cause of mortality in a mouse model of infectious colitis

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Diarrhea as a cause of mortality in a mouse model of infectious colitis

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Title: Diarrhea as a cause of mortality in a mouse model of infectious colitis
Author: Borenshtein, Diana; Fry, Rebecca C; Groff, Elizabeth B; Nambiar, Prashant R; Fox, James G; Schauer, David B; Carey, Vincent James

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Citation: Borenshtein, Diana, Rebecca C. Fry, Elizabeth B. Groff, Prashant R. Nambiar, Vincent J. Carey, James G. Fox, and David B. Schauer. 2008. Diarrhea as a cause of mortality in a mouse model of infectious colitis. Genome Biology 9(8): R122.
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Abstract: Background: Comparative characterization of genome-wide transcriptional changes during
infection can help elucidate the mechanisms underlying host susceptibility. In this study,
transcriptional profiling of the mouse colon was carried out in two cognate lines of mice that differ
in their response to Citrobacter rodentium infection; susceptible inbred FVB/N and resistant outbred
Swiss Webster mice. Gene expression in the distal colon was determined prior to infection, and at
four and nine days post-inoculation using a whole mouse genome Affymetrix array.
Results: Computational analysis identified 462 probe sets more than 2-fold differentially expressed
between uninoculated resistant and susceptible mice. In response to C. rodentium infection, 5,123
probe sets were differentially expressed in one or both lines of mice. Microarray data were
validated by quantitative real-time RT-PCR for 35 selected genes and were found to have a 94%
concordance rate. Transcripts represented by 1,547 probe sets were differentially expressed
between susceptible and resistant mice regardless of infection status, a host effect. Genes
associated with transport were over-represented to a greater extent than even immune responserelated
genes. Electrolyte analysis revealed reduction in serum levels of chloride and sodium in
susceptible animals.
Conclusion: The results support the hypothesis that mortality in C. rodentium-infected susceptible
mice is associated with impaired intestinal ion transport and development of fatal fluid loss and
dehydration. These studies contribute to our understanding of the pathogenesis of C. rodentium and
suggest novel strategies for the prevention and treatment of diarrhea associated with intestinal
bacterial infections.
Published Version: doi:10.1186/gb-2008-9-8-r122
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575512/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4891652
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