B6.129(Cg)-Scn10a^tm2(cre)Jwo/TjpJ

Stock number: 036564
Product name: Na_v1.8-Cre
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools, Sensorineural Research

Description

Na_v1.8-Cre knock-in/knock-out mice carry Cre recombinase under the control of the Scn10a (sodium channel, voltage-gated, type X, alpha or Na_v1.8) promoter. Cre expression is observed beginning at E14 in small diameter neurons in dorsal root, trigeminal and nodose ganglia. Mice heterozygous for the mutation can be used as a tool in pain behavior studies to delete floxed genes only in nociceptors.

Detailed description

Na_v1.8-Cre knock-in/knock-out mice carry a Cre recombinase inserted into the endogenous translation start site of the Scn10a (sodium channel, voltage-gated, type X, alpha or Na_v1.8) gene. The insertion replaces the Scn10a initiator methionine and inserts 3x transcriptional stops rendering the allele null for SCN10A expression. Scn10a encodes a voltage gated sodium channel that is expressed in a subset of sensory neurons that are primarily comprised of nociceptors. Cre recombinase activity is is observed beginning at E13/E14 in almost all small, some medium, and a few large diameter neurons in dorsal root and trigeminal ganglia. 75% of neurons from nodose ganglia have cre expression. Cre expression is absent in non-neuronal or CNS tissues. The pattern of expression continues into adulthood. Mice that are heterozygous for this knock-in/knock-out allele are viable and fertile and exhibit normal pain behavior. Mice homozygous for the mutation exhibit altered responses to pain. When crossed with a strain containing a loxP site flanked sequence of interest, the offspring are useful for generating cre-mediated targeted deletions in nociceptors.

Development

The Na_v1.8-Cre knockin/knockout allele was created by Dr. Mohammed Nassar and Dr. John N. Wood at University College London. To create the strain a targeting vector containing a Cre recombinase with the 3’ UTR (bps 6013-6448) from Scn10a, an SV40 polyadenylation signal (0.4 kb) and synthetic polyadenylation signal (0.2 kb) to end transcription, and followed by an FRT-flanked neomycin resistance cassette was inserted into the Scn10a translational start site of the Scn10a gene on chromosome 9. The insertion replaces the Scn10a initiator methionine rendering the allele null for SCN10A expression. The linearized construct was introduced into 129-derived unspecified embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Chimeric males were crossed to C57BL/6 females and the offspring crossed to mice carrying Gt(ROSA)26Sor^tm1(FLP1)Dym on a unspecified background to remove the neomycin cassette (leaving one FRT site after the last 3x transcriptional stop sites). Offspring were backcrossed to C57BL/6J for at least 5 generations. Dr. Theodore J. Price (University of Texas, Dallas) obtained the strain from Dr. Wood and maintained it on the C57BL/6J background (see SNP note below). Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

In 2021, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the males sent to The Jackson Laboratory Repository. Four of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Scn10a^tm2(cre)Jwo
Name: targeted mutation 2, John N Wood
MGI accession ID: MGI:3053096
Generation method: Targeted
Attributes: Recombinase-expressing
Synonyms: NaV1.8^Cre; Nav1.8Cre; nav1.8-cre; Scn10a^tm2(cre)Jnw
Marker symbol: Scn10a
Marker name: sodium channel, voltage-gated, type X, alpha
Marker synonyms: FEPS2; Na(V)1.8; Nav1.8; PN3; SNS
Chromosome: 9
Strain of origin: 129
Molecular note: Cre recombinase, 3' UTR of Scn10a, and an FRT flanked neo were knocked into the initiator methionine so that Cre replaced the ATG. Crossing with mice expressing Flp recombinase in the germ line excised the floxed neo. Cre expression was observed beginning at embryonic day 14 in small-diameter neurons in dorsal root, trigeminal, and nodose ganglia but absent in nonneuronal and CNS tissues.