Intestinal dysplasia and adenoma in transgenic mice after overexpression of an activated beta-catenin

Mutations in the adenomatous polyposis coil gene or activating mutations in the beta-catenin gene itself are thought to be responsible for the excessi ve beta-catenin signaling involved in intestinal carcinogenesis, We generat ed transgenic mice that expressed large amounts of a NH2-terminally truncat ed mutant beta-catenin (Delta N131 beta-catenin) in the intestine. These mi ce had multifocal dysplastic lesions in the small intestine, reminiscent of the early Lesions observed in the mouse models of familial adenomatous pol yposis. The number of apoptotic cells in the villi of these transgenic mice was 3-4-fold higher than in nontransgenic mice, Expression of the truncate d beta-catenin mutant in the kidney led to the development of severe polycy stic kidney disease, Our findings support the concept that deregulation of the beta-catenin sign aling pathway is the major oncogenic consequence of adenomatous polyposis c oli mutations in intestinal neoplasia.