PMID- 21704001 OWN - NLM STAT- MEDLINE DCOM- 20120120 LR - 20230603 IS - 1528-0012 (Electronic) IS - 0016-5085 (Print) IS - 0016-5085 (Linking) VI - 141 IP - 5 DP - 2011 Nov TI - Spontaneous, immune-mediated gastric inflammation in SAMP1/YitFc mice, a model of Crohn's-like gastritis. PG - 1709-19 LID - 10.1053/j.gastro.2011.06.041 [doi] AB - BACKGROUND & AIMS: Crohn's disease (CD) can develop in any region of the gastrointestinal tract, including the stomach. The etiology and pathogenesis of Crohn's gastritis are poorly understood, treatment approaches are limited, and there are not many suitable animal models for study. We characterized the features and mechanisms of chronic gastritis in SAMP1/YitFc (SAMP) mice, a spontaneous model of CD-like ileitis, along with possible therapeutic approaches. METHODS: Stomachs from specific pathogen-free and germ-free SAMP and AKR mice (controls) were evaluated histologically; the presence of Helicobacter spp was tested in fecal pellets by polymerase chain reaction analysis. In vivo gastric permeability was quantified by fractional excretion of sucrose, and epithelial tight junction protein expression was measured by quantitative reverse-transcription polymerase chain reaction analysis. The effects of a proton pump inhibitor (PPI) or corticosteroids were measured, and the ability of pathogenic immune cells to mediate gastritis was assessed in adoptive transfer experiments. RESULTS: SAMP mice developed Helicobacter-negative gastritis, characterized by aggregates of mononuclear cells, diffuse accumulation of neutrophils, and disruption of epithelial architecture; SAMP mice also had increased gastric permeability compared with controls, without alterations in expression of tight junction proteins. The gastritis and associated permeability defect observed in SAMP mice were independent of bacterial colonization and reduced by administration of corticosteroids but not a PPI. CD4(+) T cells isolated from draining mesenteric lymph nodes of SAMP mice were sufficient to induce gastritis in recipient SCID mice. CONCLUSIONS: In SAMP mice, gastritis develops spontaneously and has many features of CD-like ileitis. These mice are a useful model to study Helicobacter-negative, immune-mediated Crohn's gastritis. CI - Copyright (c) 2011 AGA Institute. Published by Elsevier Inc. All rights reserved. FAU - Reuter, Brian K AU - Reuter BK AD - Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Alberta, Canada. FAU - Pastorelli, Luca AU - Pastorelli L FAU - Brogi, Marco AU - Brogi M FAU - Garg, Rekha R AU - Garg RR FAU - McBride, James A AU - McBride JA FAU - Rowlett, Robert M AU - Rowlett RM FAU - Arrieta, Marie C AU - Arrieta MC FAU - Wang, Xiao-Ming AU - Wang XM FAU - Keller, Erik J AU - Keller EJ FAU - Feldman, Sanford H AU - Feldman SH FAU - Mize, James R AU - Mize JR FAU - Cominelli, Fabio AU - Cominelli F FAU - Meddings, Jonathan B AU - Meddings JB FAU - Pizarro, Theresa T AU - Pizarro TT LA - eng GR - R01 DK056762-09/DK/NIDDK NIH HHS/United States GR - DK056762/DK/NIDDK NIH HHS/United States GR - DK055812/DK/NIDDK NIH HHS/United States GR - P01 DK091222/DK/NIDDK NIH HHS/United States GR - R01 DK055812-13/DK/NIDDK NIH HHS/United States GR - R01 DK056762/DK/NIDDK NIH HHS/United States GR - P01 DK057880/DK/NIDDK NIH HHS/United States GR - P01 DK057880-08/DK/NIDDK NIH HHS/United States GR - DK057880/DK/NIDDK NIH HHS/United States GR - P01 DK091222-01/DK/NIDDK NIH HHS/United States GR - R56 DK055812/DK/NIDDK NIH HHS/United States GR - R01 DK055812/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110623 PL - United States TA - Gastroenterology JT - Gastroenterology JID - 0374630 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Proton Pump Inhibitors) SB - IM MH - Adrenal Cortex Hormones/therapeutic use MH - Animals MH - Crohn Disease/drug therapy/*immunology/*physiopathology MH - Disease Models, Animal MH - Feces/microbiology MH - Gastritis/drug therapy/*immunology/*physiopathology MH - Helicobacter/isolation & purification MH - Mice MH - Mice, Inbred AKR MH - Mice, Mutant Strains MH - Mice, SCID MH - Proton Pump Inhibitors/therapeutic use MH - Tight Junctions/physiology MH - Treatment Outcome PMC - PMC3197754 MID - NIHMS307665 EDAT- 2011/06/28 06:00 MHDA- 2012/01/21 06:00 PMCR- 2012/11/01 CRDT- 2011/06/28 06:00 PHST- 2011/02/10 00:00 [received] PHST- 2011/05/27 00:00 [revised] PHST- 2011/06/07 00:00 [accepted] PHST- 2011/06/28 06:00 [entrez] PHST- 2011/06/28 06:00 [pubmed] PHST- 2012/01/21 06:00 [medline] PHST- 2012/11/01 00:00 [pmc-release] AID - S0016-5085(11)00820-1 [pii] AID - 10.1053/j.gastro.2011.06.041 [doi] PST - ppublish SO - Gastroenterology. 2011 Nov;141(5):1709-19. doi: 10.1053/j.gastro.2011.06.041. Epub 2011 Jun 23.