RGD Reference Report - Kcna1-mutant rats dominantly display myokymia, neuromyotonia and spontaneous epileptic seizures. - Rat Genome Database

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Kcna1-mutant rats dominantly display myokymia, neuromyotonia and spontaneous epileptic seizures.

Authors: Ishida, S  Sakamoto, Y  Nishio, T  Baulac, S  Kuwamura, M  Ohno, Y  Takizawa, A  Kaneko, S  Serikawa, T  Mashimo, T 
Citation: Ishida S, etal., Brain Res. 2012 Jan 30;1435:154-66. doi: 10.1016/j.brainres.2011.11.023. Epub 2011 Nov 13.
RGD ID: 10047237
Pubmed: PMID:22206926   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2011.11.023   (Journal Full-text)

Mutations in the KCNA1 gene, which encodes for the alpha 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.




Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcna1Ratcell communication by electrical coupling involved_inIMP PMID:22206926UniProt 
Kcna1Ratneuronal signal transduction involved_inIMP PMID:22206926UniProt 
Kcna1Ratpotassium ion transmembrane transport involved_inIDA PMID:22206926UniProt 
Kcna1Ratregulation of muscle contraction involved_inIMP PMID:22206926UniProt 
Kcna1Ratstartle response involved_inIMP PMID:22206926UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcna1Ratcell surface  IDA  RGD 
Kcna1Ratplasma membrane located_inIDA PMID:22206926UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcna1Ratdelayed rectifier potassium channel activity enablesIDA PMID:22206926UniProt 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Kcna1  (potassium voltage-gated channel subfamily A member 1)
Kcna1Adms  (potassium voltage-gated channel subfamily A member 1;autosomal dominant myokymia and seizures)

Genes (Mus musculus)
Kcna1  (potassium voltage-gated channel, shaker-related subfamily, member 1)

Genes (Homo sapiens)
KCNA1  (potassium voltage-gated channel subfamily A member 1)

Strains
F344-Kcna1Adms/Kyo  (ADMS (autosomal dominant myokymia and seizures) rat)


Additional Information