In order to understand the importance of various cis-acting elements in regulating VP gene expression, transgenic mice regulated by VP constructs were produced containing 3.8 kb of the 5' flanking region and all the exons and introns in the mouse VP gene, which was fused at the end of exon 3 to an SV40 T antigen (Tag). In the transgenic mice by the pVPSV.IGR3.6 construct, all the six transgenic mice died at the age of 2-6 weeks. In the transgenic mice by pVPSV.IGR2.1, 21% of them had brain tumors at 5 weeks and 100% of the mice had brain tumors after 24 weeks. Histological analysis of the transgenic mice revealed primitive neuroectodermal tumors (PNET) in the brain and lymphoma in the spleen and lymph nodes. The phenotype differences between the two transgenic mice suggest that tissue-specific expression might be regulated by cis-acting elements in the 1.5-kb of the 3(') flanking region, which are not contained in pVPSV.IGR2.1. In conclusion, pVPSV.IGR2.1 mice will be a valuable mouse model system for investigating PNET tumorigenesis in the brain and lymphoma in the lymph nodes and spleen.