title: Cytodifferentiation of the postnatal mouse stomach in normal and Huntingtin-interacting protein 1-related-deficient mice.
abstract: Huntingtin-interacting protein 1-related (Hip1r) is highly expressed in gastric parietal cells, where it participates in vesicular trafficking associated with acid secretion. Hip1r-deficient mice have a progressive remodeling of the mucosa, including apoptotic loss of parietal cells, glandular hypertrophy, mucous cell metaplasia, and reduced numbers of zymogenic cells. In this study, we characterized gastric gland development in wild-type and Hip1r-deficient mice to define normal development, as well as the timing and sequence of the cellular transformation events in the mutant stomach. Postnatal (newborn to 8-wk-old) stomachs were examined by histological and gene expression analysis. At birth, gastric glands in wild-type and mutant mice were rudimentary and mature gastric epithelial cells were not apparent, although marker expression was detected for most cell lineages. Interestingly, newborns exhibited unusual cell types, including a novel surface cell filled with lipid and cells that coexpressed markers of mature mucous neck and zymogenic cells. Glandular morphogenesis proceeded rapidly in both genotypes, with gastric glands formed by weaning at 3 wk of age. In the Hip1r-deficient stomach, epithelial cell remodeling developed in a progressive manner. Initially, in the perinatal stomach, cellular changes were limited to parietal cell apoptosis. Other epithelial cell changes, including apoptotic loss of zymogenic cells and expansion of metaplastic mucous cells, emerged several weeks later when the glands were morphologically mature. Thus, parietal cell loss appeared to be the initiating event in Hip1r-deficient mice, with secondary remodeling of the other gastric epithelial cells.
authors.affiliation: Dept. of Molecular and Integrative Physiology, The Univ. of Michigan, Ann Arbor, 48109-2200, USA.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Keeley
authors.forename: Linda C
authors.initials: LC
authors.lastname: Samuelson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004848:Epithelium / Q000254:growth & development / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006706:Homeostasis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D013047:Specific Pathogen-Free Organisms; D013270:Stomach / Q000166:cytology* / Q000254:growth & development*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489534:Hip1r protein, mouse; D008840:Microfilament Proteins
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