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Floxed allele for conditional inactivation of the voltage-gated sodium channel Scn8a (NaV1.6).
Genesis. 2004 Aug; 39(4):234-9.G

Abstract

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.

Authors+Show Affiliations

Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-0618, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15286995

Citation

Levin, Stephen I., and Miriam H. Meisler. "Floxed Allele for Conditional Inactivation of the Voltage-gated Sodium Channel Scn8a (NaV1.6)." Genesis (New York, N.Y. : 2000), vol. 39, no. 4, 2004, pp. 234-9.
Levin SI, Meisler MH. Floxed allele for conditional inactivation of the voltage-gated sodium channel Scn8a (NaV1.6). Genesis. 2004;39(4):234-9.
Levin, S. I., & Meisler, M. H. (2004). Floxed allele for conditional inactivation of the voltage-gated sodium channel Scn8a (NaV1.6). Genesis (New York, N.Y. : 2000), 39(4), 234-9.
Levin SI, Meisler MH. Floxed Allele for Conditional Inactivation of the Voltage-gated Sodium Channel Scn8a (NaV1.6). Genesis. 2004;39(4):234-9. PubMed PMID: 15286995.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Floxed allele for conditional inactivation of the voltage-gated sodium channel Scn8a (NaV1.6). AU - Levin,Stephen I, AU - Meisler,Miriam H, PY - 2004/8/3/pubmed PY - 2005/3/9/medline PY - 2004/8/3/entrez SP - 234 EP - 9 JF - Genesis (New York, N.Y. : 2000) JO - Genesis VL - 39 IS - 4 N2 - 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. SN - 1526-954X UR - https://www.unboundmedicine.com/medline/citation/15286995/Floxed_allele_for_conditional_inactivation_of_the_voltage_gated_sodium_channel_Scn8a__NaV1_6__ L2 - https://doi.org/10.1002/gene.20050 DB - PRIME DP - Unbound Medicine ER -