Heart and bone tumors in transgenic mice

Tissue-specific tumorigenesis can be induced in transgenic mice by the directed expression of simian virus 40 (SV40) large tumor (T) antigen. In an attempt to determine the susceptibility of haploid, round spermatids to neoplastic transformation by this oncogene, transgenic mice were generated that harbored a chimeric gene composed of the SV40 T-antigen genes fused to the 5' and 3' flanking sequences of the mouse protamine 1 gene. The transgene was expressed in round spermatids and, suprisingly, in the heart and temporal bone as well. Expression in the heart resulted in rhabdomyosarcomas that always appeared in the right atrium. Bilateral osteosarcomas developed within the petrous portion of the temporal bone. No testicular pathology was observed. T-antigen-immunostaining was readily detected in tumor tissue but not in the testis. In addition, SV40 transcripts were processed differently in testis and tumor tissue. Transgenic mouse lines were established that routinely develop these tumors, and they should provide a valuable resource for studies involving cardiac and bone physiology and neoplasia. The atrial tumor cells can be maintained in vitro and some continue to display a cardiac muscle phenotype.