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Development of a Peptidoglycan–Polysaccharide Murine Model of Crohn's Disease: Effect of Genetic Background

Reingold, Laura*; Rahal, Kinan MD*; Schmiedlin-Ren, Phyllissa MD*; Rittershaus, Ahren C. MD; Bender, Diane PhD; Owens, Scott R. MD; Adler, Jeremy MD§; Zimmermann, Ellen M. MD*

doi: 10.1097/MIB.0b013e31828132b4
Original Basic Science Article

Abstract: The peptidoglycan–polysaccharide (PGPS) model using inbred rats closely mimics Crohn's disease. Our aim was to identify mouse strains that develop ileocolitis in response to bowel wall injection with PGPS. Mouse strains studied included NOD2 knockout animals, RICK/RIP2 knockout animals, and genetically inbred strains that are susceptible to inflammation. Mice underwent laparotomy with intramural injection of PGPS or human serum albumin in the terminal ileum, ileal Peyer's patches, and cecum. Gross abdominal score, cecal histologic score, and levels of pro-fibrotic factor mRNAs were determined 20 to 32 days after laparotomy. PGPS-injected wild-type and knockout mice with mutations in the NOD2 pathway had higher abdominal scores than human serum albumin–injected mice. The RICK knockout animals tended to have higher mean abdominal scores than the NOD2 knockout animals, but the differences were not significant. CBA/J mice were shown to have the most robust response to PGPS, demonstrating consistently higher abdominal scores than other strains. Animals killed on day 26 had an average gross abdominal score of 6.1 ± 1.5, compared with those on day 20 (3.0 ± 0.0) or day 32 (2.8 ± 0.9). PGPS-injected CBA/J mice studied 26 days after laparotomy developed the most robust inflammation and most closely mimicked the PGPS rat model and human Crohn's disease.

Article first published online 9 April 2013

*Department of Internal Medicine, Division of Gastroenterology,

Department of Pathology,

Department of Neurology, and

§Department of Pediatrics, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.

Reprints: Ellen M. Zimmermann, MD, 6520 MSRB I, SPC 5682, University of Michigan, Ann Arbor, MI (e-mail: ezimmer@umich.edu)

Supported by a grant from the National Institutes of Health (1RO1DK073992 to E.M.Z.).

The authors have no conflicts of interest to disclose.

Received August 30, 2012

Accepted September 19, 2012

© Crohn's & Colitis Foundation of America, Inc.
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