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J. Biol. Chem., Vol. 275, Issue 28, 21555-21565, July 14, 2000
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From the Departments of The H,K-ATPase of the gastric parietal cell is
the most critical component of the ion transport system mediating acid
secretion in the stomach. To study the requirement of this enzyme in
the development, maintenance, and function of the gastric mucosa, we
used gene targeting to prepare mice lacking the
Stomachs of Mice Lacking the Gastric H,K-ATPase
-Subunit Have
Achlorhydria, Abnormal Parietal Cells, and Ciliated Metaplasia*
,,¶,, and
Molecular Genetics,
Biochemistry, and Microbiology and § Environmental Health,
The University of Cincinnati College of Medicine,
Cincinnati, Ohio 45267-0524
-subunit. Homozygous
mutant (Atp4a
/) mice appeared healthy and
exhibited normal systemic electrolyte and acid-base status but were
achlorhydric and hypergastrinemic. Immunocytochemical, histological,
and ultrastructural analyses of Atp4a/
stomachs revealed the presence of chief cells, demonstrating that the
lack of acid secretion does not interfere with their differentiation.
Parietal cells were also present in normal numbers, and despite the
absence of -subunit mRNA and protein, the 
-subunit was
expressed. However, Atp4a/ parietal cells
had dilated canaliculi and lacked typical canalicular microvilli and
tubulovesicles, and subsets of these cells contained abnormal
mitochondria and/or massive glycogen stores. Stomachs of adult
Atp4a/ mice exhibited metaplasia, which
included the presence of ciliated cells. We conclude that ablation of
the H,K-ATPase -subunit causes achlorhydria and hypergastrinemia,
severe perturbations in the secretory membranes of the parietal cell,
and metaplasia of the gastric mucosa; however, the absence of the pump
appears not to perturb parietal cell viability or chief cell differentiation.
*
This work was supported by National Institutes of Health
Grant DK50594.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Molecular
Genetics, Biochemistry and Microbiology, University of Cincinnati, College of Medicine, 231 Bethesda Ave., Cincinnati, OH 45267-0524. Tel.: 513-558-0056; Fax: 513-558-1885; E-mail:
shullge@ucmail.uc.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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