TRILATERAL TUMORS IN 4 DIFFERENT LINES OF TRANSGENIC MICE EXPRESSING SV40 T-ANTIGEN

Purpose. A line of transgenic mice containing the simian virus (SV) 40 T-antigen (T-ag) gene driven by the beta-luteinizing hormone (BLH) pr omoter developed bilateral retinoblastoma and primitive neuroectoderma l tumors (PNET) of the midbrain. Midbrain tumors arose from the subepe ndymal layer of the cerebral aqueduct. Bilateral ocular and brain tumo rs (''trilateral'') were found in three other SV40 T-ag transgenic mur ine lines containing different promoters (murine interphotoreceptor re tinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin). To gain insight into the regulatory mechanisms involved in central nervo us system tumorigenesis, the authors examined brain tumors from four l ines of SV40 T-ag mice with different promoters. Methods. Formalin-fix ed brain tumors were examined from four lines of transgenic mice conta ining different promoters linked to the protein coding region of the e nhancerless SV40 T-ag oncogene. Transgenes contained the following pro moters: BLH, mouse 1.8-kb IRBP, human 1.3kb IRBP, and alpha A-crystall in. Results. Mice with a 1.8-kb IRBP promoter develop retinal photorec eptor and pineal tumors, Intracranial tumors arising from the subepend ymal layer of the third ventricle also were observed, Mice with a 1.3- kb IRBP promoter exhibit bilateral retinal PNET and PNET originating f rom the subependymal layer of the third ventricle. Mice with the alpha A-crystallin promoter exhibit bilateral lens tumors and PNET of the m idbrain. Conclusions. Ocular tumors in these mice may be ascribed to t he promoter-driven, tissue-specific expression of SV40 T-ag. The commo n finding of PNET arising from the subependymal layer of the diencepha lon is unlikely to be promoter related. These findings indicate that a regulatory region specific to the subependymal layer of the cerebral aqueduct and third ventricle resides in the structural region of the S V40 T-ag gene.