HYPERTROPHIC GASTROPATHY RESEMBLING MENETRIERS DISEASE IN TRANSGENIC MICE OVEREXPRESSING TRANSFORMING GROWTH FACTOR-ALPHA IN THE STOMACH

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 Menetrier'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 Menetrier's disease.