Floxed allele for conditional inactivation of the voltage-gated sodium channelScn8a (Nav1.6)
| Autor: | Miriam H. Meisler, Stephen I. Levin |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Transgene
Blotting Western Genetic Vectors Mutagenesis (molecular biology technique) Cre recombinase Mice Transgenic Nerve Tissue Proteins Biology Polymerase Chain Reaction Sodium Channels Mice Exon Endocrinology Genetics Animals Gene Silencing Allele Alleles DNA Primers Integrases Sodium channel Cell Biology Molecular biology Mutagenesis Insertional NAV1.6 Voltage-Gated Sodium Channel DNA Nucleotidyltransferases Gene Targeting NAV1 Cre-Lox recombination |
| Zdroj: | genesis. 39:234-239 |
| ISSN: | 1526-968X 1526-954X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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