Diarrhea as a cause of mortality in a mouse model of infectious colitis Public Deposited
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- Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
- Other Affiliation: Department of Biological Engineering, Center of Environmental Health Sciences, Massachusetts Institute of Technology, Massachusetts Avenue, Cambridge, MA 02139, USA
- AbstractBackgroundComparative 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 4 and 9 days post-inoculation using a whole mouse genome Affymetrix array. ResultsComputational 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 response-related genes. Electrolyte analysis revealed reduction in serum levels of chloride and sodium in susceptible animals. ConclusionThe 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.
- Date of publication
- August 4, 2008
- Resource type
- Rights statement
- In Copyright
- Rights holder
- Diana Borenshtein et al.; licensee BioMed Central Ltd.
- Journal title
- Genome Biology
- Journal volume
- Journal issue
- Page start
- Is the article or chapter peer-reviewed?
- Bibliographic citation
- Genome Biology. 2008 Aug 04;9(8):R122
- Open Access
- BioMed Central Ltd
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|Number of animals used for experiments.||2019-05-06||Public||
|Validation of microarray results by quantitative RT-PCR (TaqMan) on selected genes.||2019-05-06||Public||
|All differentially expressed genes.||2019-05-06||Public||
|Genes with most predictive power obtained from BioConductor analysis.||2019-05-06||Public||
|Correlation of raw intensities between biological replicates validating microarray results.||2019-05-06||Public||
|Variably expressed genes as a function of time (delta eta analysis).||2019-05-06||Public||
|Hierarchical clustering of the most differentially expressed genes with host effect.||2019-05-06||Public||
|Genes with host effect.||2019-05-06||Public||