title: 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 Xenopus oocyte 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.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor 48109-0618, USA. meislerm@umich.edu
authors.forename: M H
authors.initials: MH
authors.lastname: Meisler
authors.forename: J
authors.initials: J
authors.lastname: Kearney
authors.forename: A
authors.initials: A
authors.lastname: Escayg
authors.forename: B T
authors.initials: BT
authors.lastname: MacDonald
authors.forename: L K
authors.initials: LK
authors.lastname: Sprunger
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D009154:Mutation; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009422:Nervous System Diseases / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C100681:SCN8A protein, human; C491046:Scn8a protein, mouse; D015222:Sodium Channels