RGD Reference Report - A missense mutation of the gene encoding voltage-dependent sodium channel (Nav1.1) confers susceptibility to febrile seizures in rats. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

A missense mutation of the gene encoding voltage-dependent sodium channel (Nav1.1) confers susceptibility to febrile seizures in rats.

Authors: Mashimo, Tomoji  Ohmori, Iori  Ouchida, Mamoru  Ohno, Yukihiro  Tsurumi, Toshiko  Miki, Takafumi  Wakamori, Minoru  Ishihara, Shizuka  Yoshida, Takashi  Takizawa, Akiko  Kato, Megumi  Hirabayashi, Masumi  Sasa, Masashi  Mori, Yasuo  Serikawa, Tadao 
Citation: Mashimo T, etal., J Neurosci. 2010 Apr 21;30(16):5744-53. doi: 10.1523/JNEUROSCI.3360-09.2010.
RGD ID: 12792282
Pubmed: PMID:20410126   (View Abstract at PubMed)
PMCID: PMC6632336   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3360-09.2010   (Journal Full-text)

Although febrile seizures (FSs) are the most common convulsive syndrome in infants and childhood, the etiology of FSs has remained unclarified. Several missense mutations of the Na(v)1.1 channel (SCN1A), which alter channel properties, have been reported in a familial syndrome of GEFS+ (generalized epilepsy with febrile seizures plus). Here, we generated Scn1a-targeted rats carrying a missense mutation (N1417H) in the third pore region of the sodium channel by gene-driven ENU (N-ethyl-N-nitrosourea) mutagenesis. Despite their normal appearance under ordinary circumstances, Scn1a mutant rats exhibited remarkably high susceptibility to hyperthermia-induced seizures, which involve generalized clonic and/or tonic-clonic convulsions with paroxysmal epileptiform discharges. Whole-cell patch-clamp recordings from HEK cells expressing N1417H mutant channels and from hippocampal GABAergic interneurons of N1417H mutant rats revealed a significant shift of the inactivation curve in the hyperpolarizing direction. In addition, clamp recordings clearly showed the reduction in action potential amplitude in the hippocampal interneurons of these rats. These findings suggest that a missense mutation (N1417H) of the Na(v)1.1 channel confers susceptibility to FS and the impaired biophysical properties of inhibitory GABAergic neurons underlie one of the mechanisms of FS.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Febrile Seizures  IMP 12792282; 12792282; 12792282; 12792282; 12792282 RGD 
Febrile Seizures susceptibilityISOScn1a (Rattus norvegicus)12792282; 12792282DNA:missense mutations:cds:p.E539A and p.N1417H(rat)RGD 
Febrile Seizures  ISOScn1a (Rattus norvegicus)12792282; 12792282 RGD 
Febrile Seizures susceptibilityIMP 12792282DNA:missense mutations:cds:p.E539A and p.N1417H(rat)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased susceptibility to induction of seizure by inducing agent  IMP 12792282; 12792282; 12792282; 12792282; 12792282 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Scn1a  (sodium voltage-gated channel alpha subunit 1)
Scn1am1Kyo  (sodium voltage-gated channel alpha subunit 1; ENU induced mutant1, Kyo)
Scn1am2Kyo  (sodium voltage-gated channel alpha subunit 1; ENU induced mutant2, Kyo)

Genes (Mus musculus)
Scn1a  (sodium channel, voltage-gated, type I, alpha)

Genes (Homo sapiens)
SCN1A  (sodium voltage-gated channel alpha subunit 1)

Strains
F344-Scn1am1Kyo  (NA)
F344-Scn1am2Kyo  (NA)


Additional Information