mortality/aging
• most mice die prior to weaning, typically between 1 and 3 weeks of age
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growth/size/body
• weight is normal at birth but surviving mutants show marked growth retardation; after weaning, survivors display rapid weight gain and reach size of normal littermates by about 5 months
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digestive/alimentary system
• goblet cells are found clustered in within the crypts as well as in the villi in increased number in the duodenum and jejunum in contrast to normal littermates where goblet cells are found distributed throughout the villus in an anterior-posterior gradient in the intestine
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• at E14.5, intestinal mesenchyme has not started in invaginate to form epithelial ridges, causing delay in formation of villi; at E16.5 and E18.5, fewer, poorly-formed villi are present
• from E14.5 to 18.5, mesenchyme is less condensed than in normal littermates
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• after E16.5, intervillus regions continue to contain stratified epithelium to a greater extent than in normal embryos
• at E18.5, proliferating cells are detected in intervillus region and scattered throughout the villi in contrast to wild-type where proliferating cells are found only in intervillus region of intestinal epithelium
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• by P12, crypts appear to be expandeded and exhibit a branched morphology
• crypt compartment is expanded and disorganized by P50; abnormalities in crypt architecture are most noticeable in proximal intestine
• numbers of apoptotic cells in crypts are increased compared to controls at 50 days
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• by postnatal day 3, jejunum of mutants has fewer villi than normal controls; villi are shorter and wider than controls
• numbers of apoptotic cells in crypts are increased compared to controls at 50 days
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• at E18.5, villi are poorly formed, shorter and fewer in number compared to normal littermates
• by postnatal day 3, jejunum of mutants has fewer villi than normal controls; villi are shorter and wider than controls
• in animals >50 days of age, length of villi are increased compared to controls
• in 50 day-old animals, zone of proliferating cells is expanded corresponding to expanded crypt compartment; number of proliferating cells is increased by 4-fold compared to controls
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• at E18.5, villi are shorter than in normal littermates
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• by p3, vacuolization of surface cells and branching of glands within mucosa is observed
• subepithelial mesenchymal tissue is less dense and expanded compared to normal controls at P3; at day 50 submucosal mesenchyme is less condensed
• in adult animals, gastric mucosa is up to 6-fold thicker than normal; large cell-lined cysts and distorted mucosal glands are observed
• parietal cells show disorganized distribution while in normal controls, parietal cells are in orderly columns primarily within the isthmus and neck region of glandular epithelium
• staining for mucus cells in normal animals is strongly positive in gastric pit region but in mutants staining is strongly positive from the surface to the base of the glandular epithelium possibly to to migration of surface mucous cells throughout the gastric epithelium
• proliferating cell zone is markedly expanded throughout thickness of mucosa
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• by P3, epithelium is expanded and structure is distorted
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endocrine/exocrine glands
• by P12, crypts appear to be expandeded and exhibit a branched morphology
• crypt compartment is expanded and disorganized by P50; abnormalities in crypt architecture are most noticeable in proximal intestine
• numbers of apoptotic cells in crypts are increased compared to controls at 50 days
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neoplasm
cellular
• goblet cells are found clustered in within the crypts as well as in the villi in increased number in the duodenum and jejunum in contrast to normal littermates where goblet cells are found distributed throughout the villus in an anterior-posterior gradient in the intestine
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