Achlorhydria by ezrin knockdown: defects in the formation/expansion of apical canaliculi in gastric parietal cells.
Loss of gastric acid secretion is pathologically known as achlorhydria. Acid-secreting parietal cells are characterized by abundant expression of ezrin (Vil2), one of ezrin/radixin/moesin proteins, which generally cross-link actin filaments with plasma membrane proteins. Here, we show the direct in vivo involvement of ezrin in gastric acid secretion. Ezrin knockout (Vil2(-/-)) mice did not survive >1.5 wk after birth, making difficult to examine gastric acid secretion. We then generated ezrin knockdown (Vil2(kd/kd)) mice by introducing a neomycin resistance cassette between exons 2 and 3. Vil2(kd/kd) mice born at the expected Mendelian ratio exhibited growth retardation and a high mortality. Approximately 7% of Vil2(kd/kd) mice survived to adulthood. Ezrin protein levels in Vil2(kd/kd) stomachs decreased to <5% of the wild-type levels without compensatory up-regulation of radixin or moesin. Adult Vil2(kd/kd) mice suffered from severe achlorhydria. Immunofluorescence and electron microscopy revealed that this achlorhydria was caused by defects in the formation/expansion of canalicular apical membranes in gastric parietal cells.
Tamura
Atsushi
A
Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Kikuchi
Shojiro
S
Hata
Masaki
M
Katsuno
Tatsuya
T
Matsui
Takeshi
T
Hayashi
Hisayoshi
H
Suzuki
Yuichi
Y
Noda
Tetsuo
T
Tsukita
Shoichiro
S
Tsukita
Sachiko
S
D000126:Achlorhydria / Q000235:genetics / Q000378:metabolism*; D000143:Acids / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008871:Microvilli / Q000378:metabolism / Q000648:ultrastructure; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects / Q000648:ultrastructure; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000099149:Ezrin
D000143:Acids; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D006632:Histamine; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000099149:Ezrin; C071058:moesin; C071776:radixin