ArticleHuman molecular genetics2015
Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 160 citations in OpenAlex.
- Distinct neuronal mechanisms for motor impairment and seizures in a novel mouse model of SCN8A epileptic encephalopathy.Neurobiology of disease · 2026Article
- Zebrafish models of developmental epileptic encephalopathy accurately reflect clinical electrographic biomarkers.Epilepsia · 2026Article
- Article
- A splice-switching antisense oligonucleotide approach for pediatric genetic epilepsies.bioRxiv : the preprint server for biology · 2025Article
- Enhancing sudden unexpected death in epilepsy (SUDEP) research through development of common data elements.Epilepsia open · 2025Article
- A companion to the development of common data elements for Sudden Unexpected Death in Epilepsy (SUDEP).Epilepsia open · 2025Article
- Transgenic mouse models of sodium and potassium channelopathies in epilepsy: insights into disease mechanisms and therapeutics.Bioscience reports · 2025Review
- Persistent Na+ current couples spreading depolarization to seizures in Scn8a gain-of-function mice.Brain : a journal of neurology · 2025Article
- A research roadmap for SCN8A-related disorders: addressing knowledge gaps and aligning research priorities across stakeholders.Orphanet journal of rare diseases · 2025Article
- Seizure-related death exhibits a circadian rhythm independent of seizure timing or sleep in a mouse model of Dravet syndrome.The Journal of physiology · 2025Article
- Early mortality in STXBP1-related disorders.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Voltage-gated sodium channels in genetic epilepsy: up and down of excitability.Journal of neurochemistry · 2024Review
- Allele-Specific Editing of a Dominant SCN8A Epilepsy Variant Protects against Seizures and Lethality in a Murine Model.Annals of neurology · 2024Article
- Parvalbumin interneuron impairment causes synaptic transmission deficits and seizures in SCN8A developmental and epileptic encephalopathy.JCI insight · 2024Article
- Classification of Current Experimental Models of Epilepsy.Brain sciences · 2024Review
- Dentate gyrus granule cells are a locus of pathology in Scn8a developmental encephalopathy.Neurobiology of disease · 2024Article
- Challenges and future directions of SUDEP models.Lab animal · 2024Review
- Face-valid phenotypes in a mouse model of the most common mutation in EEF1A2-related neurodevelopmental disorder.Disease models & mechanisms · 2024Article
- Long-Term Downregulation of the Sodium Channel Gene Scn8a Is Therapeutic in Mouse Models of SCN8A Epilepsy.Annals of neurology · 2024Article
- Sex differences in physiological response to increased neuronal excitability in a knockin mouse model of pediatric epilepsy.Clinical science (London, England : 1979) · 2024Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
De novo mutations of the voltage-gated sodium channel gene SCN8A have recently been recognized as a cause of epileptic encephalopathy, which is characterized by refractory seizures with developmental delay and cognitive disability. We previously described the heterozygous SCN8A missense mutation p.Asn1768Asp in a child with epileptic encephalopathy that included seizures, ataxia, and sudden unexpected death in epilepsy (SUDEP). The mutation results in increased persistent sodium current and hyperactivity of transfected neurons. We have characterized a knock-in mouse model expressing this dominant gain-of-function mutation to investigate the pathology of the altered channel in vivo. The mutant channel protein is stable in vivo. Heterozygous Scn8a(N1768D/+) mice exhibit seizures and SUDEP, confirming the causality of the de novo mutation in the proband. Using video/EEG analysis, we detect ictal discharges that coincide with convulsive seizures and myoclonic jerks. Prior to seizure onset, heterozygous mutants are not defective in motor learning or fear conditioning, but do exhibit mild impairment of motor coordination and social discrimination. Homozygous mutant mice exhibit earlier seizure onset than heterozygotes and more rapid progression to death. Analysis of the intermediate phenotype of functionally hemizygous Scn8a(N1768D/-) mice indicates that severity is increased by a double dose of mutant protein and reduced by the presence of wild-type protein. Scn8a(N1768D) mutant mice provide a model of epileptic encephalopathy that will be valuable for studying the in vivo effects of hyperactive Nav1.6 and the response to therapeutic interventions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.