B6.129(Cg)-Scn8a^tm1Mm/J

Stock number: 039612
Product name: Scn8a^flox
Research areas: Cell Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

Scn8a^flox mice possess loxP sites flanking exon 1 of the sodium channel, voltage-gated, type VIII, alpha (Scn8a) gene. These mice may be useful for studying epilepsy.

Detailed description

Scn8a encodes the 225kda alpha subunit of the voltage-gated, type VIII sodium channel (SCN8A) involved in generation and propagation of action potentials in neurons. Gain of function mutations in the Scn8a gene have been associated with epileptic encephalopathy while loss of function mutations may lead to autism spectrum disorders (ASD), developmental delay, tremor and ataxia. These Scn8a^flox mice harbor loxP sites flanking exon 1 of the Scn8a gene.

Homozygous Scn8a^flox mice are viable and fertile with no overt phenotype. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 1 deleted in the cre-expressing tissues. The donating laboratory bred these Scn8a^flox to a ubiquitously expressing Zp3-Cre mouse line to generate Scn8a^del/del progeny. The resulting progeny (Scn8a^del/del) showed an ataxic phenotype by postnatal day 14 (PND14) followed by hindlimb paralysis. The Scn8a^del/del mice do not survive beyond 3-4 weeks of age.

Development

The Scn8a^flox targeting vector was designed to insert loxP sites flanking exon 1 of the sodium channel, voltage-gated, type VIII, alpha (Scn8a) gene on chromosome 15. The targeting construct also contained an Frt-flanked neomycin (neo) cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells and correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric mice were bred with mice expressing a FLPe recombinase, on an unknown genetic background, to remove the neo cassette. The resulting Scn8a^flox mice, with neo cassette removed and floxed exon 1 intact, were backcrossed to C57BL/6 mice for at least 10 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes.

Allele

Symbol: Scn8a^tm1Mm
Name: targeted mutation 1, Miriam Meisler
MGI accession ID: MGI:3043395
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Scn8a^flox
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: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: LoxP sites have been inserted 107 bp upstream and 134 bp downstream flanking exon 1, the first coding exon. An frt flanked neomycin resistance cassette was inserted downstream of of exon 1 as well. Mice were bred to transgenic mice expressing Flp recombinase to excise the neomycin cassette in the germ line. The resulting mice containing a floxed exon 1 were bred to homozygosity. Normal protein levels were detected by Western blot analysis.