Homozygotes can be identified by 2 weeks of age by smaller body size, ataxia, and tremor. They have progressive paralysis and die by 21 to 24 days of age. Schroeder et al. reported that no demyelination was evident in nerve cross sections, and conduction velocities were not different from age matched littermate controls at postnatal day 16. Male and female homozygous mutants display similar disease onset and progression. Molecular characterization showed this to be a C to A transversion causing an arginine to serine substitution in amino acid 914, which is in the ion pore region.
The Scn8am10J mutation arose spontaneously at The Jackson Laboratory in the FVB/NJ inbred strain in 2012 and has been maintained co-isogenic on this background ever since.
|Allele Name||mutation 10 Jackson|
|Gene Symbol and Name||Scn8a, sodium channel, voltage-gated, type VIII, alpha|
|Strain of Origin||FVB/NJ|
|Molecular Note||This spontaneous C-to-A transversion in chromosome 15 nucleotide 101,013,440 (GRCm38) causes an arginine to serine substitution at amino acid 914 (p.R914S), which is in the ion pore region of domain 2.|