Focal DEPDC5 loss without disruption to cerebral cortical neuron migration recapitulates DEPDC5-related focal epilepsy.

ABSTRACT: Focal cortical dysplasia (FCD) is a major cause of refractory epilepsy and is associated with pathogenic variants in mTOR pathway genes, including DEPDC5, the most common cause of familial focal epilepsy. The mechanisms of epileptogenesis associated with FCD and hyperactive mTOR signaling remain unclear in DEPDC5-related epilepsy. To test whether DEPDC5 loss leading to seizures requires in utero cortical developmental defects or whether postnatal neuronal dysfunction of mTORC1 is sufficient to drive seizures, we developed a postnatal focal cortical Depdc5-knockout mouse model. Postnatal day 0-1 Depdc5-floxed mice received unilateral motor cortex injections of either AAV-Cre-GFP or control AAV-GFP. The AAV-Cre-GFP-injected hemisphere had decreased DEPDC5 levels with hyperactivation of mTOR

SUBMITTER: Groff KJ 

PROVIDER: S-EPMC12643507 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature