Overactive WNT/
beta-catenin signaling has been found in many forms of
cancer in human patients. Mouse models with mutations in different components of the WNT/beta-catenin signaling pathway have been generated to mimic
tumorigenesis in humans. Mice with mutations that result in overactive WNT/
beta-catenin signaling developed
tumors in some tissues, such as digestive tract, skin, and ovary, but they failed to develop
tumors in other tissues, such as mammary gland, liver, kidney, and primordial germ cells. To investigate whether overactive
beta-catenin signaling is capable of inducing Sertoli cell
tumorigenesis in testes, we generated Ctnnb1(tm1Mmt/+);Tg(AMH-cre)1Flor male mice that express a constitutively active form of
beta-catenin specifically in Sertoli cells. No
tumors were observed at 4 mo of age, but 70% of the mutant males developed Sertoli cell
tumors at 8 mo of age. At 1 yr of age, more than 90% of the mutant males developed
tumors. No instances of extratesticular spread of the
tumors were found in the mutant mice. These studies show a causal link between overactive WNT/
beta-catenin signaling and
Sertoli cell tumor development and provide a novel mouse model for the study of
Sertoli cell tumor biology.