Targeted disruption of the murine Na+/H+ exchanger isoform 2 gene causes reduced viability of gastric parietal cells and loss of net acid secretion

Patrick J. Schultheis, Lane L. Clarke, Pierre Meneton, Matthew Harline, Gregory P. Boivin, Grant Stemmermann, John J. Duffy, Thomas Doetschman, Marian L. Miller, Gary E. Shull

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197 Scopus citations

Abstract

Multiple isoforms of the Na+/H+ exchanger (NHE) are expressed at high levels in gastric epithelium, but the physiological role of individual isoforms is unclear. To study the function of NHE2, which is expressed in mucous, zymogenic, and parietal cells, we prepared mice with a null mutation in the NHE2 gene. Homozygous null mutants exhibit no overt disease phenotype, but the cellular composition of the oxyntic mucosa of the gastric corpus is altered, with parietal and zymogenic cells reduced markedly in number. Net acid secretion in null mutants is reduced slightly relative to wild-type levels just before weaning and is abolished in adult animals. Although mature parietal cells are observed, and appear morphologically to be engaged in active acid secretion, many of the parietal cells are in various stages of degeneration. These results indicate that NHE2 is not required for acid secretion by the parietal cell, but is essential for its long-term viability. This suggests that the unique sensitivity of NHE2 to inhibition by extracellular H+, which would allow upregulation of its activity by the increased interstitial alkalinity that accompanies acid secretion, might enable this isoform to play a specialized role in maintaining the long-term viability of the parietal cell.

Original languageEnglish (US)
Pages (from-to)1243-1253
Number of pages11
JournalJournal of Clinical Investigation
Volume101
Issue number6
DOIs
StatePublished - Mar 15 1998

Keywords

  • Embryonic stem cells
  • Gene targeting
  • Ion transport
  • Mucosal protection
  • Stomach

ASJC Scopus subject areas

  • Medicine(all)

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