Achlorhydria by ezrin knockdown: defects in the formation/expansion of apical canaliculi in gastric parietal cells

oss 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 (cid:1) / (cid:1) ) mice did not survive (cid:2) 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 (cid:3) 5% of the wild-type levels without compensatory up-regulation of radixin or moesin. Adult Vil2 kd/kd mice suffered from severe achlorhydria. Immunofluores-cence and electron microscopy revealed that this achlorhydria was caused by defects in the formation/expansion of canalicular apical membranes in gastric parietal cells.