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Research Article Free access | 10.1172/JCI115936

Hypertrophic gastropathy resembling Ménétrier's disease in transgenic mice overexpressing transforming growth factor alpha in the stomach.

H Takagi, C Jhappan, R Sharp, and G Merlino

Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Find articles by Takagi, H. in: JCI | PubMed | Google Scholar

Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Find articles by Jhappan, C. in: JCI | PubMed | Google Scholar

Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Find articles by Sharp, R. in: JCI | PubMed | Google Scholar

Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Find articles by Merlino, G. in: JCI | PubMed | Google Scholar

Published September 1, 1992 - More info

Published in Volume 90, Issue 3 on September 1, 1992
J Clin Invest. 1992;90(3):1161–1167. https://doi.org/10.1172/JCI115936.
© 1992 The American Society for Clinical Investigation
Published September 1, 1992 - Version history
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Abstract

Transforming growth factor alpha (TGF alpha) is thought to participate in the normal and pathologic processes of numerous tissues, including the gastric mucosa. To explore its role in vivo, transgenic mice were generated overexpressing TGF alpha in the stomach. TGF alpha induced dramatic structural and functional lesions of the glandular stomach that were similar to Ménétrier's disease in humans. Transgenic mice developed severe adenomatous hyperplasia that resulted in a striking nodular thickening or hypertrophy of the gastric mucosa. Secretions obtained from affected stomachs contained no detectable gastric acid, suggesting that parietal cell function had been greatly impaired. These findings demonstrate that overproduction of TGF alpha can stimulate cellular proliferation, suppress acid secretion, and perturb organogenesis of the stomach of transgenic mice. Moreover, TGF alpha may contribute to the pathogenesis of related human hypertrophic gastropathies, such as Ménétrier's disease.

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