Floxed allele for conditional inactivation of the voltage-gated sodium channel Scn8a (NaV1.6).
The sodium channel gene Scn8a encodes the channel NaV1.6, which is widely distributed in the central and peripheral nervous system. NaV1.6 is the major channel at the nodes of Ranvier in myelinated axons. Mutant alleles of mouse Scn8a result in neurological disorders including ataxia, tremor, paralysis, and dystonia. We generated a floxed allele of Scn8a by inserting loxP sites around the first coding exon. The initial targeted allele containing the neo-cassette was a severe hypomorph. In vivo deletion of the neo-cassette by Flp recombinase produced a floxed allele that generates normal expression of NaV1.6 protein. Ubiquitous deletion of the floxed exon by Cre recombinase in ZP3-Cre transgenic mice produced the Scn8a(del) allele. The null phenotype of Scn8a(del) homozygotes confirms the in vivo inactivation of Scn8a. Conditional inactivation of the floxed allele will make it possible to circumvent the lethality that results from complete loss of Scn8a in order to investigate the physiologic role of NaV1.6 in subpopulations of neurons.
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-0618, USA.
Stephen I
SI
Levin
Miriam H
MH
Meisler
D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D004254:DNA Nucleotidyltransferases; D017931:DNA Primers; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D019426:Integrases; D051379:Mice; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional / Q000379:methods; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics*
D017931:DNA Primers; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels; C045073:Cre recombinase; D004254:DNA Nucleotidyltransferases; C045119:FLP recombinase; D019426:Integrases