Mapt deletion fails to rescue premature lethality in two models of sodium channel epilepsy

Abstract

Deletion of Mapt, encoding the microtubule-binding protein Tau, prevents disease in multiple genetic models of hyperexcitability. To investigate whether the effect of Tau depletion is generalizable across multiple sodium channel gene-linked models of epilepsy, we examined the Scn1b^-/- mouse model of Dravet syndrome, and the Scn8a^N1768D/+ model of Early Infantile Epileptic Encephalopathy. Both models display severe seizures and early mortality. We found no prolongation of survival between Scn1b^-/-,Mapt^+/+ , Scn1b^-/-,Mapt^+/-, or Scn1b^-/-,Mapt^-/- mice or between Scn8a^N1768D/+,Mapt^+/+ , Scn8a^N1768D/+,Mapt^+/- , or Scn8a^N1768D/+,Mapt^-/- mice. Thus, the effect of Mapt deletion on mortality in epileptic encephalopathy models is gene specific and provides further mechanistic insight.