neoplasm
• total number of azoxymethane (AOM)-induced adenocarcinomas per colon is slightly higher than in wild-type, however no mutants died after AOM treatment compared to 20% f wild-type
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• all mice older than 20 months of age exhibit intramucosal dysplasia and most older mice have intramucosal carcinomas
• majority of mice followed up to 20 months of age develop gastric carcinomas that invade the submucosa, muscularis, and vasculature
• however, no evidence of metastases to lymph nodes or other tissues is seen
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• mice infected with Heliobacter felis at 4 weeks of age exhibit accelerated progression to gastric carcinoma, with 85% developing intramucosal carcinoma, with submucosal invasion in 54% of mice, and intravascular invasion in 46% of mice
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homeostasis/metabolism
• mice initially show mild hypergastrinemia that develops into moderate hypergastrinemia with age
(J:59575)
• blood levels of gastrin are higher than in wild-type
(J:63579)
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• total number of azoxymethane (AOM)-induced adenocarcinomas per colon is slightly higher than in wild-type, however no mutants died after AOM treatment compared to 20% f wild-type
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digestive/alimentary system
• mice exhibit intestinal metaplasia at 20 months of age
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• mice develop foveolar hyperplasia and thickened gastric folds
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• small increase in the number of enterochromaffin-like (ECL) cells at 1 month of age
• ECL cell numbers decrease by 12 months of age and show an altered distribution with increasing numbers in the upper half of the gastric glands
• hypertrophy of the oxyntic glands at 20 months of age, caused primarily by foveolar hyperplasia
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• increase in the number of parietal cells at 2 and 3 months of age
• parietal cell numbers decrease to less than 68% of normal by 10 months of age and less than 40% of normal by 12 months and only a small number of parietal cells are present at 20 months
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• expansion of surface mucous cells in the gastric pit region leading to an overall increase in mucosal thickness
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• mice exhibit gastric hypertrophy at 20 months of age; hypertrophy involves only the fundus of the stomach
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• mice exhibit a 2-3-fold increase in stimulated gastric acid secretion at 1 and 4 months of age
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• mice 5 months and older show a decline in the level of stimulated acid secretion, with significantly lower level of acid secretion at 12 months of age and no acid secretion at 20 months of age
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endocrine/exocrine glands
• small increase in the number of enterochromaffin-like (ECL) cells at 1 month of age
• ECL cell numbers decrease by 12 months of age and show an altered distribution with increasing numbers in the upper half of the gastric glands
• hypertrophy of the oxyntic glands at 20 months of age, caused primarily by foveolar hyperplasia
|
• increase in the number of parietal cells at 2 and 3 months of age
• parietal cell numbers decrease to less than 68% of normal by 10 months of age and less than 40% of normal by 12 months and only a small number of parietal cells are present at 20 months
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
stomach cancer | DOID:10534 |
OMIM:613659 |
J:59575 |