B6(C3Fe)-Scn8a^8J/Frk

Stock number: 012945
Product name: Scn8a^8J
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Homozygous mutants exhibit a high incidence of spike wave discharges (SWD), impaired motor function, unsteady gait, and small size. This mutant mouse strain may be useful in studies of human absence epilepsy.

Detailed description

Scn8a is a voltage-gated, type VIII sodium channel involved in electrical signaling between cells. The 8J allele is a point mutation located in the pore region of domain 2. On a mixed C57BL/6J and C3HeB/FeJ background, mice homozygous for the mutation exhibit a high incidence of spike wave discharges (SWD), impaired motor function, unsteady gait, and small size. SWD burst frequency is recorded at 4-5 Hz. Homozygous mice die by 21 days of age, although with ground pellets some may live to 7 weeks. In mixed background heterozygotes, the SWD burst frequency is 7-9 Hz. SWD are characterized by high amplitude, significant duration and high frequency and occur between periods of locomotor activity. Severity of the SWD phenotype is dependent on genetic background. Homozygosity for C3HeB/FeJ alleles increases severity, while homozygosity for C57BL/6J alleles decreases severity. This mutant mouse strain may be useful in studies of human absence epilepsy.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

This phenotypic deviant was identified following multidose ethylnitrosourea (ENU) treatments to induce mutations in male founder C57BL/6J mice during a forward genetic screen for recessive neurological phenotypes at the ReproGenomics Facility at The Jackson Laboratory. Mutagenized males were outcrossed to C3HeB/FeJ females. Progeny were backcrossed to C57BL/6J mice for 13 generations. The mutation results in a G to T transversion in exon 13, altering the corresponding amino acid from valine to phenylalanine at codon 929 (V929F) located in the pore region of domain 2. The strain was cryopreserved in 2012.

Allele

Symbol: Scn8a^8J
Name: 8 Jackson
MGI accession ID: MGI:3806790
Generation method: Chemically induced (ENU)
Synonyms: Scn8a^V929F; V929F
Marker symbol: Scn8a
Marker name: sodium channel, voltage-gated, type VIII, alpha
Marker synonyms: ataxia 3; BFIS5; C630029C19Rik; CERIII; CIAT; DEE13; EIEE13; med; mnd2; mnd-2; motor end-plate disease; MYOCL2; NaCh6; Nav1.6; nmf2; nmf335; nmf58; nur14; PN4; seal
Chromosome: 15
Strain of origin: C57BL/6J
Molecular note: ENU mutagenesis induced a G to T transition at position 2785 that results in the amino acid substitution of phenylalanine for valine at position 929 (V929F). This substitution occurs in the pore region of the protein.