Gastric H(+),K(+)-adenosine triphosphatase beta subunit is required for normal function, development, and membrane structure of mouse parietal cells.
OBJECTIVE
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 beta subunit to determine the role of the protein in the biosynthesis of this membrane system and the biology of gastric mucosa.


METHODS
Mice deficient in the H(+), K(+)-ATPase beta subunit were produced by gene targeting.


RESULTS
The stomachs of H(+),K(+)-ATPase beta subunit-deficient mice were achlorhydric. Histological and immunocytochemical analyses with antibodies to the H(+),K(+)-ATPase alpha subunit revealed that parietal cell development during ontogeny was retarded in H(+), K(+)-ATPase beta subunit-deficient mice. In 15-day-old 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(+)-ATPase beta 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 micrometer in diameter) and contained few microvilli. We did not observe typical tubulovesicular membranes in any parietal cell from H(+),K(+)-ATPase beta subunit-deficient mice. Histopathologic alterations were only observed in the stomach.


CONCLUSIONS
The H(+),K(+)-ATPase beta 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.
Scarff
K L
KL
Department of Pathology and Immunology, Monash University Medical School, Alfred Hospital, Melbourne, Victoria, Australia.
Judd
L M
LM
Toh
B H
BH
Gleeson
P A
PA
Van Driel
I R
IR
D000818:Animals; D005753:Gastric Mucosa / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D005755:Gastrins / Q000097:blood; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D010295:Parietal Cells, Gastric / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D012313:RNA / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005755:Gastrins; D012313:RNA; D017506:H(+)-K(+)-Exchanging ATPase