Ptk2 ablation in a Trp53fl/fl, Ptenfl/fl, Rb1fl/fl mouse brain tumor model

Ptk2 was identified as a targetable genetic vulnerability in glioblastoma (GBM) cells. Our objective was to test the effect of Ptk2 deletion on survival and tumor phenotype in a mouse model of GBM. At P0, mice carrying Trp53fl/fl (Trp53tm1Brn, JAX #008462), Ptenfl/fl (Ptentm1Hwu/J, JAX #006440), Rb1fl/fl and R26-LSL-Cas9-GFP (JAX #026175) alleles were subjected to stereotactic injection to deliver lentiviral particles expressing Cre and either Ptk2-targeting or control gRNAs to the NSCs residing in the lateral subventricular zone. This injection initiates a GBM tumor in the mice. At time of sacrifice, tumor tissue was harvested and RNA was extracted for sequencing. RNA was harvested from 3 Ptk2-gRNA tumors and 3 control-gRNA (TIGRE) tumors. Gene expression profiling and differential expression analysis were conducted.