SMOOTH-MUSCLE AND BONE NEOPLASMS IN TRANSGENIC MICE EXPRESSING SV40 T-ANTIGEN

Transgenic mice carrying the SV40 early region fused to the Drosophila hsp70 promoter developed smooth muscle and bone neoplasms. The smooth muscle tumors appeared in aged mice and were preferentially located o n the muzzle or eyelids. Multiple neoplasms were often present and eac h appeared to be an independent proliferation. In contrast, the bone t umors typically developed in the petrous ridge and had all the feature s of osteogenic sarcomas, displaying distant metastasis and invasion o f the brain. Cells in both types of tumors exhibited nuclear expressio n of SV40 T antigen. Mice homozygous for the transgene had a shorter l atency for appearance of smooth muscle tumors and developed osteosarco mas more frequently than hemizygous mice. This model system implicates the cellular T antigen-binding proteins, such as Rb and p53, in the p athogenesis of bone and soft tissue neoplasms in mice.