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

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.