digestive/alimentary system
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• at 6 months of age profound epithelial hyperplasia is seen in the squamocolumnar junction
• at 12-15 months of age, 90% of mice display severe columnar metaplasia with mucus producing cells in the squamocolumnar junction
• treatment with 0.2% deoxycholate accelerates the development of Barrett-like metaplasia in the squamocolumnar junction
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• at 20-22 months of age about 20% of mice develop high-grade dysplasia or intramucosal esophageal adenocarcinoma
• at 20-22 months of age lesions are grossly visible within the distal end of the esophagus
• mutant esophagi show circumferential erythema and edema with inflammatory exudates compared to the normal esophagus and changes are made more severe by treatment with 0.2% deoxycholate
• expansion of gastric cardia progenitor cells in the esophagus over time
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• markedly thickened with a mix of acute and chronic inflammatory infiltrate
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• markedly thickened forestomach with a mix of acute and chronic inflammatory infiltrate
• increase in proliferation in the esophageal basal compartment
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• mix of acute and chronic inflammatory infiltrate
• treatment with 0.2% deoxycholate induced more severe esophagitis with inflammatory infiltrates in mutant mice compared to wild-type controls
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neoplasm
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• mice treated with 0.2% deoxycholate and N-methyl-N-nitrosourea show increased esophageal tumor development compared to wild-type controls
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• at 20-22 months of age about 20% of mice develop high-grade dysplasia or intramucosal esophageal adenocarcinoma
• during the stepwise progression to cancer there is a gradual increase in alpha SMA+ stromal myofibroblasts and increasing stroma global hypomethylation
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immune system
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• elevated IL6 in the tongue, esophagus, and forestomach but not in the stomach
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• mix of acute and chronic inflammatory infiltrate in the forestomach
• at 6 months of age moderate inflammation is seen in the squamocolumnar junction
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• mix of acute and chronic inflammatory infiltrate
• treatment with 0.2% deoxycholate induced more severe esophagitis with inflammatory infiltrates in mutant mice compared to wild-type controls
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homeostasis/metabolism
growth/size/body
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• at 20-22 months, associated with gross esophageal lesions
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hematopoietic system