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PMID:10862789
Citation |
Kobayashi, T, Tonai, S, Ishihara, Y, Koga, R, Okabe, S and Watanabe, T (2000) Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor-deficient mice. J. Clin. Invest. 105:1741-9 |
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Abstract |
To clarify the physiological roles of histamine H2 receptor (H2R), we have generated histamine H2R-deficient mice by gene targeting. Homozygous mutant mice were viable and fertile without apparent abnormalities and, unexpectedly, showed normal basal gastric pH. However, the H2R-deficient mice exhibited a marked hypertrophy with enlarged folds in gastric mucosa and an elevated serum gastrin level. Immunohistochemical analysis revealed increased numbers of parietal and enterochromaffin-like (ECL) cells. Despite this hypertrophy, parietal cells in mutant mice were significantly smaller than in wild-type mice and contained enlarged secretory canaliculi with a lower density of microvilli and few typical tubulovesicles in the narrow cytoplasm. Induction of gastric acid secretion by histamine or gastrin was completely abolished in the mutant mice, but carbachol still induced acid secretion. The present study clearly demonstrates that H2R-mediated signal(s) are required for cellular homeostasis of the gastric mucosa and normally formed secretory membranes in parietal cells. Moreover, impaired acid secretion due to the absence of H2R could be overcome by the signals from cholinergic receptors. |
Links |
PubMed PMC378512 Online version:10.1172/JCI9441 |
Keywords |
Animals; DNA/analysis; Fertility; Gastric Acid/physiology; Gastric Mucosa/pathology; Gastric Mucosa/physiology; Gastric Mucosa/physiopathology; Homozygote; Hypertrophy; Mice; Mice, Knockout; Organ Size; Receptors, Histamine H2/deficiency; Receptors, Histamine H2/genetics; Receptors, Histamine H2/physiology; Restriction Mapping; Reverse Transcriptase Polymerase Chain Reaction |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
MOUSE:HRH2 |
involved_in |
GO:0048565: digestive tract development |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2182949 |
P |
Seeded From UniProt |
complete | |
MOUSE:HRH2 |
involved_in |
GO:0003382: epithelial cell morphogenesis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2182949 |
P |
Seeded From UniProt |
complete | |
MOUSE:HRH2 |
involved_in |
GO:0001697: histamine-induced gastric acid secretion |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2182949 |
P |
Seeded From UniProt |
complete | |
MOUSE:HRH2 |
involved_in |
GO:0001698: gastrin-induced gastric acid secretion |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2182949 |
P |
Seeded From UniProt |
complete | |
See also
References
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