Scn4b floxed mice may be useful for studying the role of sodium channel beta subunits on the gating properties of sodium channels.
Gregg E Homanics, University of Pittsburgh
Scn4b floxed mice possess loxP sites flanking exon 2 of the sodium channel, type IV, beta (Scn4b) gene. SCN4B encodes a sodium channel beta subunit, expressed in the dorsal and ventral striatum, that interacts with voltage-gated alpha subunits to alter the gating properties of sodium channels. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 2 deleted in the cre-expressing tissues.
For example, when bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J (Stock No. 003724) expressing germline Cre Recombinase, resulting Scn4b KO offspring show a reduction of spike-timing-dependent long-term depression (tLTD) in medium spiny neurons (MSNs), with no effect on long-term potentiation (tLTP). These changes in action potential reduce the ability of backpropagating action potentials to evoke calcium signals in dendrites of MSNs.
A targeting vector was designed to insert a loxP site, followed by a frt-flanked neomycin resistance (neo) cassette, upstream of exon 2, and a second loxP site downstream of exon 2 of the sodium channel, type IV, beta (Scn4b) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6NCrl embryos and resulting chimeric males were bred to C57BL/6J females. Offspring were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 005703) to delete the neo cassette. Progeny were bred to C57BL/6J mice to remove the Flp-expressing transgene, resulting in a colony of Scn4b floxed mice. These mice were backcrossed to C57BL/6J mice for at least 3 more generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1.1, Gregg E Homanics|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Scn4b, sodium channel, type IV, beta|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A targeting vector was designed to insert a loxP site, followed by a FRT-flanked neomycin resistance (neo) cassette, upstream of exon 2, and a second loxP site downstream of exon 2. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 2 floxed.|
When maintaining a live colony, homozygous mice may be bred together.
When using the Scn4b floxed mouse strain in a publication, please cite the originating article(s) and include JAX stock #027530 in your Materials and Methods section.