Lymphotropic papovavirus early region is specifically regulated transgenic mice and efficiently induces neoplasia

Abstract

Transgenic mice have been generated which carry the early region of lymphotropic papovavirus (LPV). Eight of eleven founder animals died before 3 months of age after developing one or both of two distinct proliferative disorders. Of the three surviving animals, two are known to have rearranged or partial copies of the LPV genes. The majority of the founder animals (six) developed debilitating choroid plexus tumors by 26 to 42 days. Although this is the same tumor type induced by the simian virus 40 T-antigen gene, those induced by LPV appeared at a much younger age. The LPV early region was expressed in the brain tumors of these mice, as well as in the thymus and spleen. Expression in the latter two tissues reflects the cell-type specificity of the LPV enhancer demonstrated in cultured cells (i.e., lymphoid cells). Two founder animals (LP41 and LP50) gave rise to lines of mice that routinely develop lymphoproliferative disorders. LP50 and its LPV-positive offspring developed aggressive lymphomas and choroid plexus tumors. The transgenic offspring of LP41 also developed lymphomas. High levels of LPV RNA were expressed in the lymphomas of these mice as well as in the spleens and thymuses. The origin of the lymphomas from B- and T-cell lineages suggests that the LPV early genes are expressed in and can transform both of these cell types in vivo.