Parietal cells of the gastric mucosa contain a complex and extensive secretory membrane system that harbors gastric H⁺,K⁺-adenosine triphosphatase (ATPase), the enzyme primarily responsible for acidification of the gastric lumen. We have produced mice deficient in the H⁺,K⁺-ATPase β subunit to determine the role of the protein in the biosynthesis of this membrane system and the biology of gastric mucosa.

Mice deficient in the H⁺,K⁺-ATPase β subunit were produced by gene targeting.

The stomachs of H⁺,K⁺-ATPase β subunit–deficient mice were achlorhydric. Histological and immunocytochemical analyses with antibodies to the H⁺,K⁺-ATPase α subunit revealed that parietal cell development during ontogeny was retarded in H⁺,K⁺-ATPase β subunit–deficient mice. In 15-day-old mice, cells with secretory canaliculi were observed in wild-type but not in H⁺,K⁺-ATPase β subunit–deficient mice. Parietal cells of H⁺,K⁺-ATPase β subunit–deficient mice 17 days and older contained an abnormal canaliculus that was dilated and contained fewer and shorter microvilli than normal. In older parietal cells, the abnormal canaliculus was massive (25 μm in diameter) and contained few microvilli. We did not observe typical tubulovesicular membranes in any parietal cell from H⁺,K⁺-ATPase β subunit–deficient mice. Histopathologic alterations were only observed in the stomach.

The H⁺,K⁺-ATPase β subunit is required for acid-secretory activity of parietal cells in vivo, normal development and cellular homeostasis of the gastric mucosa, and attainment of the normal structure of the secretory membranes. GASTROENTEROLOGY 1999;117:605-618