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National Institute of Environmental Health Sciences

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Publication Detail

Title: Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger.

Authors: Gawenis, Lara R; Greeb, Jeannette M; Prasad, Vikram; Grisham, Christina; Sanford, L Philip; Doetschman, Thomas; Andringa, Anastasia; Miller, Marian L; Shull, Gary E

Published In J Biol Chem, (2005 Apr 01)

Abstract: The NHE4 Na+/H+ exchanger is abundantly expressed on the basolateral membrane of gastric parietal cells. To test the hypothesis that it is required for normal acid secretion, NHE4-null mutant (NHE4-/-) mice were prepared by targeted disruption of the NHE4 (Slc9a4) gene. NHE4-/- mice survived and appeared outwardly normal. Analysis of stomach contents revealed that NHE4-/- mice were hypochlorhydric. The reduction in acid secretion was similar in 18-day-old, 9-week-old, and 6-month-old mice, indicating that the hypochlorhydria phenotype did not progress over time, as was observed in mice lacking the NHE2 Na+/H+ exchanger. Histological abnormalities were observed in the gastric mucosa of 9-week-old NHE4-/- mice, including sharply reduced numbers of parietal cells, a loss of mature chief cells, increased numbers of mucous and undifferentiated cells, and an increase in the number of necrotic and apoptotic cells. NHE4-/- parietal cells exhibited limited development of canalicular membranes and a virtual absence of tubulovesicles, and some of the microvilli had centrally bundled actin. We conclude that NHE4, which may normally be coupled with the AE2 Cl-/HCO3- exchanger, is important for normal levels of gastric acid secretion, gastric epithelial cell differentiation, and development of secretory canalicular and tubulovesicular membranes.

PubMed ID: 15684419 Exiting the NIEHS site

MeSH Terms: Achlorhydria/pathology; Alleles; Alternative Splicing; Animals; Apoptosis; Blotting, Northern; Blotting, Western; Cell Differentiation; DNA, Complementary/metabolism; Dose-Response Relationship, Drug; Exons; Gastric Acid/metabolism*; Gastrins/metabolism; Hydrogen-Ion Concentration; Immunoblotting; In Situ Nick-End Labeling; Mice; Mice, Transgenic; Microscopy, Electron; Models, Biological; Models, Genetic; Mutation; Necrosis; Parietal Cells, Gastric/cytology; Parietal Cells, Gastric/ultrastructure; Phenotype; RNA, Messenger/metabolism; RNA/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Sodium-Hydrogen Exchangers/metabolism; Sodium-Hydrogen Exchangers/physiology*; Time Factors

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Last Reviewed: October 02, 2024