Enhanced Intestinal Adenomatous Polyp Formation in Pms2 ' ;Min Mice1

Analysis of two human familial cancer syndromes, hereditary nonpol yposis colorectal cancer and familial adenomatous polyposis, indicates that mutations in either one of four DNA mismatch repair gene homo logues or the adenomatous polyposis coli (APC) gene, respectively, are important for the development of colorectal cancer. To further investigate the role of DNA mismatch repair in intestinal tumorigenesis, we generated mice with mutations in both Ape and the DNA mismatch repair gene, Pms2. Whereas />m«2-deficient mice do not develop intestinal tumors, mice deficient in Pms2 and heterozygous for Min, an alÃ-eleof Ape, develop approximately three times the number of small intestinal adenomas and four times the number of colon adenomas relative to Min and Pms2+'~; Min mice. Although Pms2 deficiency clearly increases adenoma formation in the Min background, histolÃ3gica! analysis indicated no clear evidence for progression to carcinoma.