Correlation Engine 2.0
Clear Search sequence regions

  • brain (4)
  • brainstem (1)
  • calcium channels (1)
  • cerebellum (1)
  • forebrain (2)
  • gene (2)
  • hippocampus (1)
  • ischemia (1)
  • mice (3)
  • patient (1)
  • potassium channels (1)
  • rna (2)
  • SCN8A (7)
  • seizures (4)
  • sodium channels (4)
  • transcript (5)
  • Sizes of these terms reflect their relevance to your search.

    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. Copyright © 2016 Elsevier Inc. All rights reserved.


    Ryan S Sprissler, Jacy L Wagnon, Rosie K Bunton-Stasyshyn, Miriam H Meisler, Michael F Hammer. Altered gene expression profile in a mouse model of SCN8A encephalopathy. Experimental neurology. 2017 Feb;288:134-141

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 27836728

    View Full Text