Sodium Channels and Neurological Disease: Insights from Scn8a Mutations in the Mouse
Abstract
The human genome contains 10 voltage-gated sodium channel genes, 7 of which are expressed in neurons of the CNS and PNS. The availability of human genome sequences and high-throughput mutation screening methods make it likely that many human disease mutations will be identified in these genes in the near future. Mutations of Scn8a in the mouse demonstrate the broad spectrum of neurological disease that can result from different alleles of the same sodium channel gene. Null mutations of Scn8a produce motor neuron failure, loss of neuromuscular transmission, and lethal paralysis. Less severe mutations result in ataxia, tremor, muscle weakness, and dystonia. The effects of Scn8a mutations on channel properties have been studied in the Xenopusoocyte expression system and in neurons isolated from the mutant mice. The Scn8a mutations provide insight into the mode of inheritance, effect on neuronal sodium currents, and role of modifier genes in sodium channel disease, highlighting the ways in which mouse models of human mutations can be used in the future to understand the pathophysiology of human disease.
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Nav1.6 functions in part to maintain a resurgent sodium current that enables regular, spontaneous firing.
“Nav1.6 functions, in part, to maintain a resurgent sodium current that enables regular, spontaneous firing.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [142]
The pace-making defect in L7-DKO mice resembles that of mice lacking the voltage-gated sodium channel subunit Scn8a.
“The pace-making defect in the L7-DKO mice is highly reminiscent of mice lacking the voltage-gated sodium channel subunit Scn8a (REFS 141–143).”
From The neurogenetics of alternative splicing (2016) · cites this paper as [142]
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- Authors
- Meisler, M. H., Kearney, J., Escayg, A., Macdonald, B. T., & Sprunger, L. K.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Meisler, Miriam H.
- Venue
- The Neuroscientist
- Publisher
- SAGE Publications
- Published
- 2001-04
- Volume
- 7
- Issue
- 2
- Pages
- 136-145
- ISSN
- 1073-8584 (ISSN-L)
- 1089-4098
- OpenAlex
- W2049969724
- Cited by
- 68
- References
- 46
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 6 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 4
- FWCI
- 0.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Neuroscientist (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM024872, GM 24872)
- National Institute of Neurological Disorders and Stroke (NS 34509, R01NS034509)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- SCN8A, voltage-gated sodium channels, sodium channel mutations, neurological disorders, mouse models of human disease, neuromuscular transmission, paralysis, ataxia, dystonia, tremor, genetic modifiers, mode of inheritance, channelopathies
- MeSH terms
- Animals, Humans, Mutation, Nerve Tissue Proteins, Nervous System Diseases, Sodium Channels, Mice, NAV1.6 Voltage-Gated Sodium Channel
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