RNA-Sequencing of USP15 knock-out mice injected with kainate

Transcriptome studies of brain resections from mesial temporal lobe epilepsy (mTLE) patients revealed a dysregulation of transforming growth factor (TGF)-ß, interferon (IFN)-a/ß and nuclear factor erythroid 2-related factor 2 (NRF2) pathways among other neuroinflammatory mechanisms. Since ubiquitin-specific proteases (USP), in particular USP15, have been shown to regulate these pathways, we hypothesized that the blockade of USP15 may provide therapeutic relief in treatment-resistant epilepsies. The intrahippocampal kainate mouse model for mTLE, an established model for pharmacoresistant epilepsy was used for validation of USP15 as a therapeutic target. Transgenic mice which constitutively lack USP15 underwent intrahippocampal kainate injections to investigate the impact of USP15 inactivation at the transcriptomic level.