To generate a mouse
glioblastoma model by genome editing, we introduced
Cas9 protein and guide RNAs specific for Nf1, Pten, and Trp53 into the neonatal mouse forebrain by electroporation. We found a high incidence (approximately 90%) of glial
tumor development, including
glioblastomas, 15 weeks later. The histological features of the
tumors were similar to those of diffuse
gliomas and, in some cases, similar to human
glioblastomas, with microvascular proliferation (glomeruloid structure). In addition, unlike
glial fibrillary acidic protein (GFAP)-positive
glioblastomas generated using a similar method in a previous model, the majority of
tumor cells were positive for oligodendrocyte lineage
transcription factor 2, but negative for GFAP and neurofilaments. One base pair insertions identical to those seen in a previous model were found around the target sequences in Nf1, Pten, and Trp53, and additional deletions were found only in Pten. Considering that the histological characteristics were different from those seen in the previous model, our new model provides an additional research tool to investigate the early stages of
glioblastoma development.