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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)12781-12789
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number13
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

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Sodium-Hydrogen Antiporter
Gastric Acid
Membranes
Acids
Chloride-Bicarbonate Antiporters
Actins
Cell Count
Genes
Cells
Achlorhydria
Gastric Parietal Cells
Gastrointestinal Contents
Microvilli
Gastric Mucosa
Cell Differentiation
Stomach
Epithelial Cells
Phenotype

ASJC Scopus subject areas

  • Biochemistry

Cite this

Gawenis, L. R., Greeb, J. M., Prasad, V., Grisham, C., Sanford, L. P., Doetschman, T. C., ... Shull, G. E. (2005). Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger. Journal of Biological Chemistry, 280(13), 12781-12789. https://doi.org/10.1074/jbc.M414118200

Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger. / Gawenis, Lara R.; Greeb, Jeannette M.; Prasad, Vikram; Grisham, Christina; Sanford, L. Philip; Doetschman, Thomas C; Andringa, Anastasia; Miller, Marian L.; Shull, Gary E.

In: Journal of Biological Chemistry, Vol. 280, No. 13, 01.04.2005, p. 12781-12789.

Research output: Contribution to journalArticle

Gawenis, LR, Greeb, JM, Prasad, V, Grisham, C, Sanford, LP, Doetschman, TC, Andringa, A, Miller, ML & Shull, GE 2005, 'Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger', Journal of Biological Chemistry, vol. 280, no. 13, pp. 12781-12789. https://doi.org/10.1074/jbc.M414118200
Gawenis, Lara R. ; Greeb, Jeannette M. ; Prasad, Vikram ; Grisham, Christina ; Sanford, L. Philip ; Doetschman, Thomas C ; Andringa, Anastasia ; Miller, Marian L. ; Shull, Gary E. / Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 13. pp. 12781-12789.
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