Konishi Shoji, Naora Hiroyuki, Kimura Minoru, Sato Masahiro, Nagasaki Makoto, Yokoyama Minesuke, Otani Hiroki, Moritake Kozo, Katsuki Motoya
Department of Neurosurgery, Shimane University, Department of Medicine, Izumo, Japan.
Congenit Anom (Kyoto). 2004 Dec;44(4):215-24. doi: 10.1111/j.1741-4520.2004.00042.x.
Primitive neuroectodermal tumors (PNET) are classified as the embryonal tumors developed in the brain, except for the cerebellum. Although many studies have been reported, the origin and pathogenesis of PNET are still unclear. In this study, we observed the development of undifferentiated tumors indistinguishable from PNET in the transgenic mice which expressed simian virus 40 T antigen (SV40-Tag) selectively in the oligodendroglia under the control of mouse myelin basic protein gene promoter. These PNET-like tumors reproducibly developed in the brain stem of the founder mice and the transgenic progeny derived from one founder mouse. Oligodendroglia-specific expression of SV40-Tag in these transgenic mice was observed by immunohistochemical analysis. Furthermore, expression of the oligodendroglia-specific marker genes was decreased in the tumors as well as in the transgenic brains. These findings suggested that tumors developed in transgenic mice were indistinguishable from PNET, and one of them showed oligodendroglia-like characteristics. Consequently, this transgenic line is a useful animal model to study the pathogenesis of undifferentiated tumor.
原始神经外胚层肿瘤(PNET)被归类为除小脑外发生于脑内的胚胎性肿瘤。尽管已有许多研究报道,但PNET的起源和发病机制仍不清楚。在本研究中,我们在小鼠髓鞘碱性蛋白基因启动子控制下,观察了在少突胶质细胞中选择性表达猿猴病毒40 T抗原(SV40-Tag)的转基因小鼠中与PNET难以区分的未分化肿瘤的发生情况。这些类PNET肿瘤在奠基小鼠的脑干以及来自一只奠基小鼠的转基因后代中可重复性地发生。通过免疫组织化学分析观察到这些转基因小鼠中SV40-Tag在少突胶质细胞中的特异性表达。此外,少突胶质细胞特异性标记基因在肿瘤以及转基因脑中的表达均降低。这些发现提示,转基因小鼠中发生的肿瘤与PNET难以区分,其中之一表现出少突胶质细胞样特征。因此,该转基因品系是研究未分化肿瘤发病机制的有用动物模型。