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Banyu Tsukuba Research Institute (Merck), 3 Okubo, Tsukuba 300-33 [M. O., H. O., M. K., M. M. T.], and Department of Oncological Pathology, Cancer Center, Nara Medical College, Kashihara, Nara 634 [M. T.], Japan
Mutations in the adenomatous polyposis coli (APC) gene are responsible for not only familial adenomatous polyposis but also many sporadic cancers of the digestive tract. Most mutations found in familial adenomatous polyposis patients are of the truncation type, and the phenotype is affected by the mutation sites in the gene. Truncated APC proteins can associate with the wild-type protein. Accordingly, it has been proposed that the polyposis is caused by a dominant negative mechanism. To test this possibility, we constructed transgenic mice that contained mutant minigenes. They expressed the APC protein truncated either at codon 716 (Apc
716) or 1287 (Apc1287) at high levels in the intestinal epithelium. Contrary to our expectation, no intestinal polyps or tumors were found in any of such mice, even after 7 months. These results rule out any dominant negative mechanisms in which the truncated APC protein is directly involved in the formation of intestinal polyps in the mouse.
1 To whom requests for reprints should be addressed.
Received 3/ 9/95. Accepted 5/19/95.
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