Floxed allele for conditional inactivation of the voltage-gated sodium channel Scn8a (Nav1.6)

Stephen I. Levin, Miriam H. Meisler*

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The sodium channel gene Scn8a encodes the channel Nav1.6, which is widely distributed in the central and peripheral nervous system. Na v1.6 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 Scn8adel allele. The null phenotype of Scn8adel hornozygotes 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.

Original languageEnglish (US)
Pages (from-to)234-239
Number of pages6
JournalGenesis
Volume39
Issue number4
DOIs
StatePublished - Aug 2004

Keywords

  • Conditional allele
  • Cre/IoxP
  • Na1.6
  • Scn8a

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

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