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.