Intestinal polyposis in mice with a dominant stable mutation of the β‐catenin gene

Ectopic expression of certain Wnt genes in mouse mammary tissue is tumorigenic, and mutations that stabilize β‐catenin are found in various human cancers including colorectal cancer. To determine the role of stabilized β‐catenin in intestinal tumorigenesis in mice, we constructed by embryonic stem (ES) cell‐mediated homologous recombination, a mutant β‐catenin allele whose exon 3 was sandwiched by loxP sequences. When the germline heterozygotes were crossed with mice expressing Cre recombinase in the intestines, the serines and threonine encoded by exon 3 and to be phosphorylated by glycogen synthase kinase 3β (GSK3β) were deleted in the offspring intestines, which caused adenomatous intestinal polyps resembling those in ApcΔ716 knockout mice. Some nascent microadenomas were also found in the colon. These results present experimental genetic evidence that activation of the Wnt signaling pathway can cause intestinal and colonic tumors.

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