Muir-Torre-like syndrome in Fhit-deficient mice

To investigate the role of the Fhit gene in carcinogen induction of neoplas ia, we have inactivated one Fhit allele in mouse embryonic stem cells and p roduced (129/SvJ x C57BL/6J) F-1 mice with a Fhit allele inactivated (+/-). Fhit +/+ and +/- mice were treated intragastrically with nitrosomethylbenz ylamine and observed for 10 wk posttreatment. A total of 25% of the +/+ mic e developed adenoma or papilloma of the forestomach, whereas 100% of the +/ - mice developed multiple tumors that were a mixture of adenomas, squamous papillomas, invasive carcinomas of the forestomach, as well as tumors of se baceous glands. The visceral and sebaceous tumors, which lacked Fhit protei n, were similar to those characteristic of Muir-Torre familial cancer syndr ome.