Development of mouse glioma model using in vivo electroporation

抄録

Glioblastoma multiforme (GBM), is one of the most malignant brain tumors, has highly-proliferative and invasive characters. To understand these malignant characters of GBM, an appropriate tumorigenesis model is required. Loss of INK4A/ARF and stimulation of common signal transduction pathways involving RAS are frequently found in GBM. Previously, we have established a stable mouse models of brain tumors, transplanting the genetically modified neural stem cells (NSCs). The NSCs derived from Ink4a/Arf KO mice, transduced activated-H-RAS, rapidly formed highly proliferative and invasive brain tumors. Recently, for the purpose of reproducing a clinical tumor initiating process, we are developing a mouse model of brain tumors by gene transfer into mouse brain directly. Using in vivo electroporation and piggyBac system, transduction of activated-RAS and shInk4a/Arf into NSCs in mouse brain, efficiently formed brain tumors have an equally malignant behavior as the transplantation model. On the basis of these findings, we propose this in vivo tumorigenesis technique is efficient method to generate appropriate mouse brain tumor models.