Regulation of gastric epithelial cell development revealed in H+/K+-ATPasebeta-subunit- and gastrin-deficient mice

The gastric H+/K+-ATPase is essential for normal development of parietal ce lls. Here we have directly assessed the role of the H+/K+-ATPase beta -subu nit (H/K-beta) on epithelial cell development by detailed quantitation of t he epithelial cell types of the gastric mucosa of H/K-beta -deficient mice. H/K-beta -deficient mice had a 3.1-fold increase in the number of immature cells per gastric unit; however, the numbers of surface mucous and parieta l cells were similar to those in the gastric units of wild-type mice. The e ffect of elevated gastrin levels in the H/K-beta -deficient mice was determ ined by producing mice that are also deficient in gastrin. We demonstrated that the increased production of immature cells and resulting hypertrophy i s caused by the overproduction of gastrin. However, the depletion of zymoge nic cells, which is another feature of H/K-beta -deficient mice, is indepen dent of hypergastrinemia. Significantly, parietal cells of H/K-beta- and ga strin-deficient mice had abnormal secretory membranes and were devoid of re sting tubulovesicular membranes. Together these data suggest a homeostatic mechanism limiting the number of immature cells that can develop into end-s tage epithelial cells and indicate a direct role for H/K-beta in the develo pment of mature parietal cells.