These conditional Scn1a-A1783V mice express the Dravet Syndrome/SMEI-associated mutation A1783V in the presence of Cre recombinase, and exhibit Dravet-like phenotypes including spontaneous seizures.
Ana Mingorance, Dravet Syndrome Foundation, Spain
Scn1a encodes the large alpha subunit of the type I voltage sensitive sodium channel essential for the generation and propagation of action potentials in nerve and muscle. Several mutations in the domain IV S6 transmembrane region, including A1783V, are associated with SMEI (severe myoclonic epilepsy in infancy) and Dravet Syndrome, a convulsive disorder with psychomotor delay, ataxia, and cognitive impairment.
When these conditional Scn1a mice are bred to mice that express cre recombinase, resulting offspring express the A1783V mutation in the cre-expressing tissues. Depending on the genetic background of the cre line used, mice display a lethal seizure phenotype at about three weeks of age: greater than 80% of heterozygotes survive with a ubiquitous cre on a 129 background, but less than 40% survive on a pure B6 background. Viable mice exhibit spontaneous seizures, motor stereotypies, and hyperactivity. This strain may be useful for studying SMEI and Dravet Syndrome.
A mini-gene cassette containing a loxP site, coding sequence for wild-type exon 26, bpA, FRT-flanked neomycin cassette, and a second loxP site was introduced into intron 25 and a A1783V mutation was introduced into exon 26. The mutation results in a C to T change at nucleotide 5348 altering the corresponding amino acid from alanine to valine at position 1783. The construct was electroporated into unspecified embryonic stem (ES) cells derived from C57BL/6J mice. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to B6.Cg-Tg(ACTFLPe)9205Dym/J (Stock No. 005703) to remove the neomycin cassette. Heterozygous mice were mated and offspring crossed to C57BL/6J for one generation. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1.1, Dravet Syndrome Foundation Spain|
|Allele Type||Targeted (Conditional ready (e.g. floxed), Humanized sequence, No functional change)|
|Allele Synonym(s)||Scn1atm1.1Dsf; targeted mutation 1.1, Dravet Syndrome Foundation Spain|
|Gene Symbol and Name||Scn1a, sodium channel, voltage-gated, type I, alpha|
|Gene Synonym(s)||Nav1.1; SMEI; HBSCI; NAC1; FEB3; FEB3A; SCN1; EIEE6; FHM3; GEFSP2|
|Strain of Origin||C57BL/6J|
|Molecular Note||A mini-gene cassette containing a loxP site, coding sequence for wild-type exon 26, bpA, an FRT-flanked neomycin cassette, and a second loxP site was introduced into intron 25 and a A1783V mutation was introduced into exon 26. The mutation results in a C to T change at nucleotide 5348 altering the corresponding amino acid from alanine to valine at position 1783.|
While maintaining a live colony, these mice are bred as heterozygotes. The donating investigator has not attempted to generate homozygous mice to date (February 2015).
When using the floxed stop Scn1a*A1783V mouse strain in a publication, please cite the originating article(s) and include JAX stock #026133 in your Materials and Methods section.
|Heterozygous or wildtype for|
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