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Achlorhydria by ezrin knockdown

Atsushi Tamura¹, Shojiro Kikuchi^1,2, Masaki Hata³, Tatsuya Katsuno¹, Takeshi Matsui³, Hisayoshi Hayashi⁴, Yuichi Suzuki⁴, Tetsuo Noda^5,6, Shoichiro Tsukita¹, and Sachiko Tsukita^1,7

¹ Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
² Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
³ KAN Research Institute, Kyoto Research Park, Shimogyo-ku, Kyoto 606-8317, Japan
⁴ Laboratory of Physiology, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
⁵ Department of Cell Biology, Cancer Institute of Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
⁶ Department of Molecular Genetics, Tohoku University School of Medicine, Seryo-cho, Aoba-ku, Sendai 980-8575, Japan
⁷ School of Health Sciences, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan

Correspondence to Sachiko Tsukita: atsukita{at}mfour.med.kyoto-u.ac.jp

Abstract

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.

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