1. Volume 141, Issue 5, Pages 1709-1719 (November 2011)
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 
Gastroenterology 
Volume 141, Issue 5, Pages (November 2011)
DOI: /j.gastro
Copyright © 2011 AGA Institute Terms and Conditions

2. Figure 1
Time course and histologic features of SAMP gastritis. (A) Gastric TIS in SAMP (white boxes) and AKR (black boxes) mice, aged 3 to 20 weeks. n = 5 to 12 per group; *P < .05 vs age-matched AKRs. (B) Representative photomicrographs demonstrate 3-week-old SAMP mice with normal gastric mucosa, while 12- and 20-week-old mice show progression of pathologic features and severity of gastritis. Twelve-week-old SAMP mice show increased acute and chronic inflammation within the lamina propria with focal glandular abscesses (arrowheads), while 20-week-old mice present with more diffuse, chronic transmural inflammatory infiltrates (corpus region depicted, left panels). AKR mice at 3 and 12 weeks have normal appearing, noninflamed stomachs, whereas 20-week-old mice show focal, minimal chronic inflammation along the base of the mucosa, consistent with normal, physiologic inflammation (right panels). Original magnification 200×. (C) Representative photomicrographs of full-thickness corpus of 20-week-old SAMP mice display a prominent inflammatory infiltrate within the mucosa and extending into the submucosa (left panel; original magnification 200×), with higher magnification of an inflammatory site consisting mostly of lymphocytes with occasional neutrophils and macrophages at the base of crypts (middle panel; original magnification 400×). Acute and chronic inflammation highlighting foci of active gastritis with neutrophils present within the glandular epithelium; focal crypt abscess (arrowhead) is depicted (right panel; original magnification 400×). (D) Prevalence and severity of SAMP gastritis in different age groups; n = 16 to 78 per group. (E) Severity of gastritis in male and female SAMP mice at different age groups. n = 8 to 42 per group; no significant differences in gastritis severity comparing male with female mice were detected. (F) Correlation analysis of gastric and ileal TIS showed a significant positive correlation between these 2 phenotypes. n = 147; r = 0.412, P <
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2011 AGA Institute Terms and Conditions

3. Figure 2
Quantitative and qualitative assessment of MPO activity in SAMP gastritis. (A) MPO activity was determined in gastric tissue samples from SAMP (white boxes) and AKR (black boxes) mice aged 3 to 20 weeks. MPO activity and (B) MPO immunoreactivity (corpus region depicted) was highest in 3-week-old SAMP and AKR mice. Original magnification 200×. (C) Assessment of gastric permeability (sucrose fractional excretion) in SAMP mice showed early and increased permeability compared with age-matched AKRs, while (D) young SAMP mice (3 to 4 weeks old) demonstrated elevated levels of CXCL1 mRNA transcripts compared with age-matched AKRs. n = 5 to 18 per group for all experiments; *P < .05 versus age-matched AKR.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2011 AGA Institute Terms and Conditions

4. Figure 3
Development of SAMP gastritis occurs in the absence of bacterial flora colonization and is likely mediated by an inherent epithelial barrier defect. (A) Both SPF and GF SAMP mice displayed increased gastric permeability at 3 to 4 weeks, before and/or coincident with the onset of gastric inflammation, compared with age-matched SPF AKRs, as measured by (B) histologic examination and (C) MPO activity. n = 6 to 30 per group for all experiments; *P < .05 versus age-matched SPF AKR mice; ΨP < .05 versus age-matched GF SAMP mice. (D) Severity and histologic features of gastritis in 3- to 4-week-old and older than 20-week-old SAMP mice raised under GF conditions. GF SAMP mice at an early age show diffuse acute and chronic inflammation, present mostly within the lamina propria. Older GF SAMP mice display acute and chronic inflammation within the base of the lamina propria with superficial, mucosal clear cell metaplasia. Original magnification: 150× (upper panels) and 100× (lower panels).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2011 AGA Institute Terms and Conditions

5. Figure 4
Epithelial TJ protein expression in SAMP stomachs before the onset of gastritis. Representative photomicrographs of corpus tissue from 3- to 4-week-old SAMP and AKR mice immunostained for (A) occludin or (B) claudin-5 demonstrate that their distribution appears unaltered, both in the upper and lower portions of the gastric glands of SAMP compared with age-matched AKRs. Original magnification 200×. (C) Quantitative RT-PCR for claudin-5, -3, and -18 and occludin mRNA transcripts was performed on full-thickness corpus tissues obtained from young (3- to 4-week-old) AKR and SAMP mice. No significant alterations in gene expression for the TJ proteins measured were detected. Data are normalized to 18S ribosomal RNA and presented as mean ± SEM (n = 7–8 per group).
Gastroenterology  , DOI: ( /j.gastro )
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6. Figure 5
Decreased gastric inflammation in SAMP mice treated with corticosteroids but not a PPI. Ten-week-old SAMP mice with established gastritis were treated with either the PPI pantoprazole (50 mg/kg orally) or dexamethasone (5 mg/kg intraperitoneally). (A) Treatment with pantoprazole had no effect on gastric inflammation but increased gastric paracellular permeability. Conversely, (B) treatment with dexamethasone reduced both gastritis (left panel) as well as gastric paracellular permeability (right panel). n = 6 per group (histologic evaluation), *P < .05 versus vehicle; n = 6 per group (permeability studies), *P < .05 versus pretreatment.
Gastroenterology  , DOI: ( /j.gastro )
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7. Figure 6
Pathogenic SAMP CD4+ T lymphocytes mediate gastritis when transferred into naïve SCID mice. Six weeks after transfer, SCIDs receiving SAMP CD4+ T cells developed mild to moderate gastritis as determined by (A) histologic evaluation and (B) MPO activity. (C) Representative histology and immunohistochemical staining for MPO demonstrate the majority of inflammation and cellular infiltrates localized to the corpus region of the stomach in SCIDs receiving donor SAMP cells. Minimal to no inflammation was found in gastric tissues obtained from SCIDs adoptively transferred with AKR CD4+ T lymphocytes. Original magnification 100×. n = 8 per group; **P < .01 and *P < .05 vs control (SCIDs with no cell transfer) and AKR (SCIDs receiving donor AKR CD4+ T cells). (D) Full-thickness corpus tissues from SCIDs adoptively transferred with SAMP donor CD4+ T cells display increased Th1, Th2, and IL-17F cytokine mRNA transcripts compared with SCID recipients of AKR donor cells. Data are presented as fold differences with AKR (SCIDs receiving donor AKR CD4+ T cells) average values set as 1. n = 5 to 6 per group; *P < .05 and ***P < .005.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2011 AGA Institute Terms and Conditions