SV40 T Antigen Directed by a Powerful Erythroid Enhancer–Promoter Produced Sarcomas and Pancreatic Tumors But Not Erythroid-Specific Tumors in Transgenic Mice

Abstract

We have expressed the simian virus 40 (SV40) large T antigen oncogene in erythroid tissues of mice to test its ability to immortilize erythroid cells. A transgene construct was built in which the SV40 large T antigen structural gene was linked to erythroid-specific enhancer and promoter sequences. The enhancer employed was the human β-globin family microlocus control region, and the promoter sequences were derived from the human β-globin promoter. Transgenic mice were generated and they expressed T antigen in the bone marrow and spleen cells. Yet, no hematopoietic neoplasia arose in these mice. Instead, after a lag period of 2–6 months, the mice developed soft tissue sarcomas and pancreatic islet-cell tumors that expressed high levels of T antigen.