Abstract
We previously reported that transgenic mice produced with a transgene consisting of the SV40 T antigen and vasopressin without the 3'-flanking region exhibit brain tumors and lymphoma. In this study, transgenic mice were produced with the fusion gene containing the SV40 T antigen and the whole vasopressin gene with the 3'-flanking region. Six transgenic mice were generated, five which died after 2-6 weeks. The remaining founder mouse was investigated for fusion gene expression and tumor progression at the age of 6 weeks. Brain tumor cells were characterized for phenotypes and transgene expression. During in vitro cell cultures, the phenotypic appearances at 10, 20, and 30 passages were as a uniform monolayer with similar growth rates. The site of SV40 T antigen integration was in the A2 region of chromosome 11, and SV40 T antigen was expressed at the same level in cells of both earlier and later passages. Thirty passages were probably insufficient to reach crisis and immortalization. These cells enriched brain tumor cell compositions with astrocytes and neuronal cells.
Highlights
We previously reported the generation of transgenic mice via microinjection of the fusion gene consisting of the SV40 T antigen and mouse vasopressin (VP) without the 3'-flanking region (Lee et al, 2003)
Characterization of the brain tumor cell line derived from the midbrain tumor Tumor tissues that were isolated from the surviving founder transgenic mouse were dispersed and maintained in culture for several months (Figure 2)
No tumors resulted when SV40 T antigen gene transformed cells were injected into nude mice, which suggests that this cell line was still in a premalignant stage
Summary
We previously reported the generation of transgenic mice via microinjection of the fusion gene (pVPSV.IGR2.1) consisting of the SV40 T antigen and mouse vasopressin (VP) without the 3'-flanking region (Lee et al, 2003). Of these mice, 21% developed brain tumors at 5 weeks and the remaining mice developed brain tumors after 24 weeks. The PNETs of the central nervous system are a family of brain tumors and embryonic malignant tumors that account for 20% of all midbrain tumors in children These tumors are characterized by primitive histological features resembling neuroepithelial stem cells from the embryonic neural tube or immature progeny (Lee et al, 2003). PVPSV.IGR2.1 transgenic mice died after 24 weeks with tumors in the brain so this model is not useful for study of tumor progression
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