Long-term gastric changes in achlorhydric H⁺/K⁺-ATPase beta subunit deficient mice

Abstract

Objective. Hypergastrinemia is known to induce enterochromaffin-like (ECL) cell derived tumors in rodents and man. In this study, we have examined the effect of life-long gastric anacidity and secondary hypergastrinemia in H⁺/K⁺-ATPase beta subunit knockout (KO) mice. Material and methods. Female H⁺/K⁺-ATPase beta subunit KO mice and controls were followed up to 20 months before being sacrificed. At termination, intragastric acidity was measured and internal organs were examined for macroscopic and histological changes. Plasma gastrin and serum albumin were measured. Results. KO mice were anacidic and hypergastrinemic. The oxyntic mucosa was markedly, and with increase in age, hyperplastic with cystic dilatations resembling the changes seen in patients with Menetrier's disease. Serum albumin in KO mice did not differ from controls. KO mice had a marked ECL cell hyperplasia, but only one gastric carcinoma was found. Conclusion. H⁺/K⁺-ATPase beta subunit KO mice develop Menetrier-like changes in the stomach, and may be useful in studying the pathogenesis and treatment of Menetrier's disease. The reason why only one KO mice developed gastric neoplasia whereas the histamine-2 blocker loxtidine has previously been found to regularly induce ECL cell carcinoids in mice is not known.

Key Words::

• ECL cell
• gastric cancer
• gastrin
• Menetrier's disease
• proton pump inhibitors

Acknowledgement

We thank Prof. I. van Driel for providing H⁺/K⁺-ATPase beta subunit deficient mice.

Declaration of interest: The study was supported by the Norwegian Gastroenterological Association.The authors alone are responsible for the content and writing of the paper.