GASTRIC-LESIONS IN TRANSFORMING GROWTH-FACTOR-BETA-1 HETEROZYGOUS MICE

Transforming growth factor beta-1 (TGF beta 1) is known to inhibit the growth of many epithelial cell types in culture. Consequently, it is important to determine whether it has any tumor suppressor activity in vitro. Fifteen heterozygous and eight wild type TGF beta 1-deficient mice were examined to determine if there was a difference in lifespan or lesion development due to the loss of one TGF beta 1 allele. Mice w ere killed when there was evidence of neoplasia or severe illness. The re was no significant difference in the lifespan of the two groups. Hy perplastic lesions in the glandular mucosa were seen in 10 TGF beta 1 (+/-) mice. These lesions were localized to the lesser curvature of th e stomach, extending from the limiting ridge to the pylorus. Seven of the 10 glandular hyperplastic lesions in the TGF beta 1 (+/-) mice had features similar to human gastritis cystica profunda. Associated with the glandular invasion of the muscularis were a mixed inflammatory in filtration of the surrounding muscular wall and mucosa with chronic va sculitis in the tissues adjacent to these lesions. In contrast to the distinct genotypic differences in lesion incidence observed in the gla ndular stomach, there was no significant difference in lesion incidenc e in other organs. The increased incidence of the hyperplastic lesions in the TGF beta 1 (+/-) mice is highly suggestive that allelic loss o f TGF beta 1 plays an important role in the genesis of these lesions. However, allelic loss of TGF beta 1 does not cause alterations in the incidence of neoplasia.