Spontaneous, immune-mediated gastric inflammation in SAMP1/YitFc mice, a model of Crohn's-like gastritis

Brian K. Reuter, Luca Pastorelli, Marco Brogi, Rekha R. Garg, James A. McBride, Robert M. Rowlett, Marie C. Arrieta, Xiao Ming Wang, Erik J. Keller, Sanford H. Feldman, James R. Mize, Fabio Cominelli, Jonathan B. Meddings, Theresa T. Pizarro

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1709-1719
Number of pages11
JournalGastroenterology
Volume141
Issue number5
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Epithelial Permeability
  • Germ-Free
  • Inflammatory Bowel Disease
  • Stomach

ASJC Scopus subject areas

  • Gastroenterology

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