Mice homozygous for the Scn1a (voltage gated sodium channel) knockout allele exhibit tremors, ataxia, seizures and die by postnatal day 16. Heterozygous mice on the 129S6/SvEvTac background do not exhibit an overt phenotype, however, on the C57BL/6 background mice develop spontaneous seizures and die within weeks. This strain may be useful for genetic analysis of epilepsy and Dravet syndrome.
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Jennifer Kearney, Vanderbilt University
Scn1a encodes the alpha subunit of a heteromeric complex forming the voltage sensitive sodium channel. Mutations in SCN1A are associated with several epilepsy syndromes including Dravet Syndrome, an infant-onset epileptic encephalopathy. Mice homozygous for this null allele exhibit tremors, ataxia and seizures; death occurs by postnatal day 16. Heterozygous mice on the C57BL/6 background develop spontaneous seizures and die within weeks. On an F1 hybrid (C57BL/6J x 129S6/SvEvTac) background, heterozygotes exhibit an intermediate phenotype including seizures and a 50% lethality by one month of age. On the 129S6/SvEvTac background, mice do not exhibit an overt phenotype; lifespan is normal and no seizures are recorded by EEG monitoring. This strain may be useful for genetic analysis of epilepsy and Dravet syndrome.
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.
A targeting vector containing a loxP-flanked PGKneo cassette was used to replace exon 1. The construct was electroporated into 129S6/SvEvTac-derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129S6/SvEvTac mice and maintained as a cross to 129S6/SvEvTac at every generation. Upon arrival, mice were bred to 129S1/SvImJ mice (Stock No. 002448) for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Jennifer Kearney|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Scn1a, sodium channel, voltage-gated, type I, alpha|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A loxP-flanked neomycin resistance cassette replaced the first coding exon. Absence of protein was confirmed by immunoblotting.|
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation die by postnatal day 16.
When using the SCN1A knockout mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37107 in your Materials and Methods section.