Altered gene expression profile in a mouse model of SCN8A encephalopathy

Ryan S. Sprissler, Jacy L. Wagnon, Rosie K. Bunton-Stasyshyn, Miriam H. Meisler, Michael F. Hammer

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Nav1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures. The abundance of 50 transcripts increased more than 3-fold and 15 transcripts decreased more than 3-fold after seizures. The elevated transcripts included two anti-convulsant neuropeptides and more than a dozen genes involved in reactive astrocytosis and response to neuronal damage. There was no change in the level of transcripts encoding other voltage-gated sodium, potassium or calcium channels. Reactive astrocytosis was observed in the hippocampus of mutant mice after seizures. There is considerable overlap between the genes affected in this genetic model of epilepsy and those altered by chemically induced seizures, traumatic brain injury, ischemia, and inflammation. The data support the view that gain-of-function mutations of SCN8A lead to pathogenic alterations in brain function contributing to encephalopathy.

Original languageEnglish (US)
Pages (from-to)134-141
Number of pages8
JournalExperimental Neurology
StatePublished - Feb 1 2017


  • Astrocyte
  • Epileptic encephalopathy
  • Gene expression
  • RNA-seq
  • Seizure
  • Sodium channel
  • Transcriptome

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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