C3Fe.B6-Scn8a^8J/Frk

Stock number: 012946
Research areas: Developmental Biology Research, Neurobiology Research

Description

Mice with this mutation of the sodium channel, voltage-gated, type VIII, alpha (Scn8a) gene exhibit a high incidence of spike wave discharges (SWD) and may be useful studies of human absence epilepsy.

Detailed description

Mice that are homozygous for this chemically-induced allele exhibit small size, a weak and unsteady gait and a high incidence of spike wave discharges (SWD). On a mixed C57BL/6J and C3HeB/FeJ background, SWD burst frequency is recorded at 4-5 Hz. Homozygous mice die by 21 days, however, with additional care (see husbandry), mice can survive 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. 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 missense point mutation was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males in the ReproGenomics facility at The Jackson Laboratory. Mutagenized males were outcrossed to C3HeB/FeJ females; descendants of the mutagenized males were selected for neurological impairment. The mutation results in an G to T change at nucleotide 2785 altering the corresponding amino acid from phenylalanine to valine at position 929 (V929F) in domain 2 of the protein's pore region. This strain has been backcrossed to C3HeB/FeJ for a minimum of 12 generations.

Allele

Symbol: Scn8a^8J
Name: 8 Jackson
MGI accession ID: MGI:3806790
Generation method: Chemically induced (ENU)
Marker symbol: Scn8a
Marker name: sodium channel, voltage-gated, type VIII, alpha
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.