Development, characterization and transcriptional profiling of a mouse model of fatal infectious diarrhea and colitis

Citrobacter rodentium is a naturally occurring murine bacterial pathogen which is used to model human diarrheagenic E. coli (EPEC and EHEC) infections in mice. C. rodentium causes colonic hyperplasia and a variable degree of colitis and mortality in the majority of inbred and outbred lines of mice. Differences in C. rodentium-induced disease are determined by the genetic background of the host. Here, C. rodentium infection in resistant outbred Swiss Webster (SW) mice was compared with infection in the cognate inbred FVB strain for the first time. In contrast to subclinical infection in SW mice, adult FVB mice developed overt disease with significant weight loss, severe colitis, and over 75% mortality. Fluid therapy intervention completely prevented mortality in FVB mice, and expression of pro-inflammatory and immunomodulatory genes in the colon was similar in both lines of mice, suggesting that mortality in C. rodentiuminfected FVB mice is due to hypovolemia resulting from severe dehydration. To identify host factors responsible for the development of mortality, gene expression in the distal colon of FVB and SW mice was investigated using a whole mouse genome Affymetrix array.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Borenshtein, Diana

Advisor dc:contributor.advisor

• David B. Schauer.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/39843

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/39843