Gastric H+,K+-adenosine triphosphatase beta subunit is required for normalfunction, development, and membrane structure of mouse parietal cells

Background & Aims: Parietal cells of the gastric mucosa contain a complex a nd extensive secretory membrane system that harbors gastric H+,K+-adenosine triphosphatase (ATPase), the enzyme primarily responsible for acidificatio n of the gastric lumen. We have produced mice deficient in the H+,K+-ATPase beta subunit to determine the role of the protein in the biosynthesis of t his membrane system and the biology of gastric mucosa. Methods: Mice defici ent in the H+,K+-ATPase beta subunit were produced by gene targeting. Resul ts: The stomachs of H+,K+-ATPase beta subunit-deficient mice were achlorhyd ric. Histological and immunocytochemical analyses with antibodies to the H,K+-ATPase alpha subunit revealed that parietal cell development during ont ogeny was retarded in H+,K+-ATPase beta subunit-deficient mice. In 15-day-o ld mice, cells with secretory canaliculi were observed in wild-type but not in H+,K+-ATPase beta subunit-deficient mice. Parietal cells of H+,K+-ATPas e beta subunit-deficient mice 17 days and older contained an abnormal canal iculus that was dilated and contained fewer and shorter microvilli than nor mal. In older parietal cells, the abnormal canaliculus was massive (25 mu m in diameter) and contained few microvilli. We did not observe typical tubu lovesicular membranes in any parietal cell from H+,K+-ATPase beta subunit-d eficient mice. Histopathologic alterations were only observed in the stomac h. Conclusions: The H+,K+-ATPase beta subunit is required for acid-secretor y activity of parietal cells in vivo, normal development and cellular homeo stasis of the gastric mucosa, and attainment of the normal structure of the secretory membranes.