Referenced in: none

Automatically associated channels: Nav1.6

Title: Ion channel mutations in mouse models of inherited neurological disease.

Authors: M H Meisler, L K Sprunger, N W Plummer, A Escayg, J M Jones

Journal, date & volume: Ann. Med., 1997 Dec , 29, 569-74

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9562526

Abstract
Analysis of the molecular defects in mouse mutants can identify candidate genes for human neurological disorders. During the past 2 years, mutations in sodium channels, calcium channels and potassium channels have been identified by positional cloning of the spontaneous mouse mutants motor endplate disease, tottering, lethargic and weaver. The phenotypes of four allelic mutations identified in the sodium channel gene Scn8a range from ataxia and muscle weakness through severe dystonia and progressive paralysis, indicating that human mutations in this gene could be associated with a variety of clinical syndromes. Mutations of the calcium channel subunits beta 4 in the lethargic mouse and alpha 1A in the tottering mouse have specific effects on cerebellar function. Targeted mutation of ligand-gated ion channels has also been used to generate new models of neurological disease. We will review these recent achievements and their implications for human neurological disease. The mouse studies indicate that mutations in ion channel genes are likely to be responsible for a broad spectrum of clinical phenotypes in human neurological disorders.