GASTRIC-MUCOSA ABNORMALITIES AND TUMORIGENESIS IN MICE LACKING THE PS2 TREFOIL PROTEIN

To determine the function of the pS2 trefoil protein, which is normall y expressed in the gastric mucosa, the mouse pS2 (mpS2) gene was inact ivated, The antral and pyloric gastric mucosa of mpS2-null mice was dy sfunctional and exhibited severe hyperplasia and dysplasia. All homozy gous mutant mice developed antropyloric adenoma, and 30 percent develo ped multifocal intraepithelial or intramucosal carcinomas. The small i ntestine was characterized by enlarged villi and an abnormal infiltrat e of lymphoid cells. These results indicate that mpS2 is essential for normal differentiation of the antral and pyloric gastric mucosa and m ay function as a gastric-specific tumor suppressor gene.