title: Allelic mutations of the sodium channel SCN8A reveal multiple cellular and physiological functions.
abstract: Allelic mutations of Scn8a in the mouse have revealed the range of neurological disorders that can result from alternations of one neuronal sodium channel. Null mutations produce the most severe phenotype, with motor neuron failure leading to paralysis and juvenile lethality. Two less severe mutations cause ataxia, tremor, muscle weakness, and dystonia. The electrophysiological effects have been studied at the cellular level by recording from neurons from the mutant mice. The data demonstrate that Scn8a is required for the complex spiking of cerebellar Purkinje cells and for persistent sodium current in several classes of neurons, including some with pacemaker roles. The mouse mutations of Scn8a have also provided insight into the mode of inheritance of channelopathies, and led to the identification of a modifier gene that affects transcript splicing. These mutations demonstrate the value of mouse models to elucidate the pathophysiology of human disease.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0618, USA. meislerm@umich.edu
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Meisler
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Plummer
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Burgess
authors.forename: David A
authors.initials: DA
authors.lastname: Buchner
authors.forename: Leslie K
authors.initials: LK
authors.lastname: Sprunger
mesh_terms: D000483:Alleles; D000818:Animals; D051379:Mice; D009046:Motor Neurons / Q000502:physiology; D018908:Muscle Weakness / Q000235:genetics; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D017433:Protein Structure, Secondary; D011689:Purkinje Cells; D015222:Sodium Channels / Q000235:genetics* / Q000502:physiology*
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels