1. Volume 131, Issue 6, Pages 1844-1855 (December 2006)
A Mouse Model of Hereditary Pancreatitis Generated by Transgenic Expression of R122H Trypsinogen 
Herbert Archer, Natalia Jura, James Keller, Matthew Jacobson, Dafna Bar–Sagi 
Gastroenterology 
Volume 131, Issue 6, Pages (December 2006)
DOI: /j.gastro
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2. Figure 1
Transgene construct and expression analysis. (A) Schematic representation of the R122H_mPRSS1 transgene construct. Ela, elastase promoter; Tr, trypsinogen; UTR, untranslated region. (B) Immunohistochemical detection of acinar-specific transgene expression using anti-FLAG antibody (original magnification 100× and 400×). (Inset, bottom right panel in B) The granular localization of FLAG-trypsin in R122H_mPRSS1 mice. (C) Real-time RT-PCR analysis of the relative expression levels of the transgene in R122H_mPRSS1 animals of different ages. The average value obtained for 4 wild-type animals was subtracted from expression level obtained for each transgenic animal.
Gastroenterology  , DOI: ( /j.gastro )
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3. Figure 2
Acinar cell necrosis is an early manifestation of the phenotype in R122H_mPRSS1 transgenic mice. (A) H&E image of the wild-type pancreas showing normal acinar (ac) and duct (d) structures (original magnification 100×). (B) Representative H&E image from a 7-week-old R122H_mPRSS1 animal indicates increased vacuolization of the acinar cells (original magnification 200×). (C) Immunohistochemical staining for apoptotic cells with anti-cleaved caspase-3 antibody in the pancreata of R122H_mPRSS1 mice (original magnification 200×). (D and E) Immunohistochemical staining for necrotic cells with anti-HMG1 antibody in (D) wild-type and (E) R122H_mPRSS1 mice (original magnification 200×). Arrows point to the nuclear accumulation of HMGB-1 in the wild-type animal and its cytosolic translocation in the transgenic mouse.
Gastroenterology  , DOI: ( /j.gastro )
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4. Figure 3
R122H_mPRSS1 transgenic mice develop inflammatory lesions. (A) Intra-acinar inflammation (arrow) in the pancreata of 16-week-old mice (original magnification 200×). (B) Immunohistochemical analysis showing positive Flag staining (arrows) in association with inflammation (asterisk) (original magnification 200×). (C) A fibrotic region in 1-year-old R122H_mPRSS1 mice (original magnification 50×). (D) Immunohistochemical staining for α–smooth muscle actin in a fibrotic lesion from a 1-year-old R122H_mPRSS1 mouse (original magnification 100×). (E) Trichrome staining (blue) indicates deposition of collagen in the areas of fibrosis in a 1-year-old R122H_mPRSS1 mouse (original magnification 200×). Insets represent higher magnifications of selected areas in the corresponding images. (F) Quantitative analysis of the inflammatory phenotype observed in R122H_mPRSS1 animals. Data are presented as percent of the animals that display fibrotic lesions in the indicated age group. Wild-type mice, gray bars; R122H_mPRSS1 mice, black bars; n, number of animals within the age group. Wild-type animals used in this experiment had the same genetic background as transgenic animals. The statistical significance of the differences was calculated using the Fisher exact test (*P < .05).
Gastroenterology  , DOI: ( /j.gastro )
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5. Figure 4
Characterization of the inflammatory infiltrates in R122H_mPRSS1 mice. (A) A representative H&E image of an inflammatory infiltrate from an R122H_mPRSS1 mouse (original magnification 100×). Immunohistochemical staining of R122H_mPRSS1 inflammatory infiltrates for (B) the common leukocyte antigen CD-45, (C) the T-cell specific marker CD-3, (D) the B-cell specific marker B220, (E) the macrophage specific marker F4-80, and (F) a proinflammatory cytokine, TNF-α. Insets represent higher magnifications of selected areas in the corresponding images.
Gastroenterology  , DOI: ( /j.gastro )
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6. Figure 5
The effect of cerulein administration on R122H_mPRSS1 mice. Representative H&E images of sections obtained from (A and C) wild-type and (B and D) R122H_mPRSS1 mice at (A and B) 1 day and (C and D) 1 week after cessation of cerulein treatment (original magnification 100×). (E and F) Assessment of fibrotic reaction in (E) wild-type and (F) R122H_mPRSS1 mice by trichrome staining for collagen (blue) (original magnification 200×). (G) Morphometric quantitation of fibrosis in the wild-type (light gray bars) and R122H_mPRSS1 mice (dark gray bars) at 1 day and 1 week after cerulein injection. Error bars represent SEM; differences between experiments were examined using Student t test (*P < .05).
Gastroenterology  , DOI: ( /j.gastro )
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7. Figure 6
Inflammation induces compartment-specific activation of signaling pathways in pancreata of R122H_mPRSS1 mice. Evaluation of the extent of activation of JNK, NF-κB, and ERK signaling pathways by immunohistochemical analysis of (A–C) c-jun (original magnification 400×), (D–F) p65 (original magnification 400×), and (G–I) pERK (original magnification 100×) expression pattern in pancreata of 6–12-month-old R122H_mPRSS1 animals and age-matched controls.
Gastroenterology  , DOI: ( /j.gastro )
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8. Figure 7
Chronic inflammatory lesions in R122H_mPRSS1 mice. (A) A representative H&E image of intralobular inflammation and fibrosis in a 1-year-old R122H_mPRSS1 animal (original magnification 100×). (B) Immunohistochemical assessment of acinar cell proliferation in a fibrotic area from the R122H_mPRSS1 mouse using proliferating cell nuclear antigen as a marker (original magnification 400×). Note the cytosolic staining of proliferating cell nuclear antigen, which represents cells that entered mitosis (arrow). (C and D) Selected areas from A are shown at higher magnification (original magnification 400×). Note the decreased apical cell height (arrowhead) and the enlargement of the acinar lumen (arrow). (E) Immunohistochemical staining for the acinar cell marker amylase (original magnification 400×). (F) Immunohistochemical staining for the ductal cell marker cytokeratin 19 (original magnification 200×). Arrows point to the cytokeratin 19–negative tubular structures.
Gastroenterology  , DOI: ( /j.gastro )
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