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


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.


CONCLUSIONS
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.
Bakkelund
Karin E
KE
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Waldum
Helge L
HL
Nordrum
Ivar Skjåk
IS
Hauso
Øyvind
Ø
Fossmark
Reidar
R
D000126:Achlorhydria / Q000150:complications*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D005758:Gastritis, Hypertrophic / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D013997:Time Factors