Floxed allele for conditional inactivation of the voltage-gated sodium channel Scn8a (Na v 1.6)

Abstract

The sodium channel gene Scn8a encodes the channel Na V 1.6, which is widely distributed in the central and peripheral nervous system. Na V 1.6 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 Na V 1.6 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 Na V 1.6 in subpopulations of neurons. genesis 39:234–239, 2004. © 2004 Wiley-Liss, Inc.