RRC ID 27754
著者 Ishida S, Sakamoto Y, Nishio T, Baulac S, Kuwamura M, Ohno Y, Takizawa A, Kaneko S, Serikawa T, Mashimo T.
タイトル Kcna1-mutant rats dominantly display myokymia, neuromyotonia and spontaneous epileptic seizures.
ジャーナル Brain Res
Abstract Mutations in the KCNA1 gene, which encodes for the α subunit of the voltage-gated potassium channel Kv1.1, cause episodic ataxia type 1 (EA1). EA1 is a dominant human neurological disorder characterized by variable phenotypes of brief episodes of ataxia, myokymia, neuromyotonia, and associated epilepsy. Animal models for EA1 include Kcna1-deficient mice, which recessively display severe seizures and die prematurely, and V408A-knock-in mice, which dominantly exhibit stress-induced loss of motor coordination. In the present study, we have identified an N-ethyl-N-nitrosourea-mutagenized rat, named autosomal dominant myokymia and seizures (ADMS), with a missense mutation (S309T) in the voltage-sensor domain, S4, of the Kcna1 gene. ADMS rats dominantly exhibited myokymia, neuromyotonia and generalized tonic-clonic seizures. They also showed cold stress-induced tremor, neuromyotonia, and motor incoordination. Expression studies of homomeric and heteromeric Kv1.1 channels in HEK cells and Xenopus oocytes, showed that, although S309T channels are transferred to the cell membrane surface, they remained non-functional in terms of their biophysical properties, suggesting a dominant-negative effect of the S309T mutation on potassium channel function. ADMS rats provide a new model, distinct from previously reported mouse models, for studying the diverse functions of Kv1.1 in vivo, as well as for understanding the pathology of EA1.
巻・号 1435
ページ 154-66
公開日 2012-1-30
DOI 10.1016/j.brainres.2011.11.023
PII S0006-8993(11)02074-9
PMID 22206926
MeSH Animals Antiemetics / therapeutic use Biophysical Phenomena / genetics Biotinylation Body Weight / drug effects Carbamazepine / therapeutic use Cells, Cultured Chromosome Mapping DNA Mutational Analysis Disease Models, Animal Electric Stimulation Electroencephalography Electromyography Epilepsy / chemically induced Epilepsy / drug therapy Epilepsy / genetics* Epilepsy / mortality Ethylnitrosourea / toxicity Gene Transfer Techniques Humans Isaacs Syndrome / chemically induced Isaacs Syndrome / genetics* Isaacs Syndrome / mortality Kv1.1 Potassium Channel / drug effects Kv1.1 Potassium Channel / genetics* Male Membrane Potentials / drug effects Membrane Potentials / genetics Mice Models, Molecular Mutagenesis / drug effects* Mutagens / toxicity Mutation, Missense / drug effects* Mutation, Missense / genetics Myokymia / chemically induced Myokymia / genetics* Myokymia / mortality Oocytes Patch-Clamp Techniques Protein Transport / genetics Psychomotor Performance / physiology Rats Rats, Inbred F344 Rats, Mutant Strains Sequence Analysis Serine / genetics Survival Analysis Swimming Threonine / genetics Time Factors Xenopus
IF 2.733
引用数 23
WOS 分野 NEUROSCIENCES
リソース情報
ラット F344-Adms/Kyo(strainID=724)