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Gene Review

Scn8a  -  sodium channel, voltage-gated, type VIII,...

Mus musculus

Synonyms: AI853486, C630029C19Rik, NMF335, NaCh6, Nav1.6, ...
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Disease relevance of Scn8a


High impact information on Scn8a

  • Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease' [2].
  • Scn8a is expressed in brain and spinal cord but not in skeletal muscle or heart, and encodes a predicted protein of 1,732 amino acids [2].
  • Expression of CD69, an early activation marker, is first observed on a minority of cells at the T cell receptor (TCR)lo/med double-positive stage, is maximal (50-90%) on heat-stable antigen (HSA)hi TCRhi double-positive, HSAhi TCRmed CD4+8lo, and HSAhi TCRhi CD4+8- cells, and is downmodulated at the mature HSAlo CD4+8- stage [6].
  • Sodium currents and action potentials were characterized in Purkinje neurons from ataxic mice lacking expression of the sodium channel Scn8a [7].
  • In jolting mice, with a missense mutation in Scn8a, steady-state and resurgent current were also reduced, with altered voltage dependence and kinetics [7].

Biological context of Scn8a

  • We previously reported that the phenotype of the hypomorphic allele of Scn8a, medJ, is dependent upon an unlinked modifier locus, Scnm1 [1].
  • Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3 [8].
  • Our results suggest that at least a portion of the dmu phenotype is caused by a down-regulation of Scn8a, making dmu a new allele of Scn8a [9].
  • The generation of three independent Scn8a mutations among 1100 tested G3 families demonstrates that the Scn8a locus is highly susceptible to ENU mutagenesis [10].
  • We also recorded non-sodium currents from Purkinje cells of both genotypes to test whether the Scn8a mutation induced changes in other ion channels [11].

Anatomical context of Scn8a


Associations of Scn8a with chemical compounds


Other interactions of Scn8a

  • Using fluorescence in situ hybridization (FISH), the Mgat3 gene was regionally mapped to chromosome 15E11, near the Scn8a sodium channel gene at 15F1 [21].
  • Analysis of a transgene-induced mutation at the mouse med locus led to the identification of the novel voltage-gated sodium channel gene Scn8a (Burgess, D. L., Kohrman, D. C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B., and Meisler, M. H.(1995) Nat. Genet. 10, 461-465) [16].
  • This reduction was not an unspecific consequence of muscle disease, as it was not observed in two other neuromuscular mouse mutants, "wobbler" (wr) and "motor endplate disease" (med or medjo) [22].
  • Synaptotagmin 1 and contactin 1 were eliminated as candidate genes for the med mutation [23].
  • Coexpression of the beta1 and beta2 subunits modulated the properties of Scn8a channels, but to a lesser extent than for the Rat1 or Rat2 channels [13].

Analytical, diagnostic and therapeutic context of Scn8a


  1. Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Na(v)1.6). Kearney, J.A., Buchner, D.A., De Haan, G., Adamska, M., Levin, S.I., Furay, A.R., Albin, R.L., Jones, J.M., Montal, M., Stevens, M.J., Sprunger, L.K., Meisler, M.H. Hum. Mol. Genet. (2002) [Pubmed]
  2. Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'. Burgess, D.L., Kohrman, D.C., Galt, J., Plummer, N.W., Jones, J.M., Spear, B., Meisler, M.H. Nat. Genet. (1995) [Pubmed]
  3. Paranodal dysmyelination and increase in tetrodotoxin binding sites in the sciatic nerve of the motor end-plate disease (med/med) mouse during postnatal development. Rieger, F., Pinçon-Raymond, M., Lombet, A., Ponzio, G., Lazdunski, M., Sidman, R.L. Dev. Biol. (1984) [Pubmed]
  4. Dysregulation of axonal sodium channel isoforms after adult-onset chronic demyelination. Rasband, M.N., Kagawa, T., Park, E.W., Ikenaka, K., Trimmer, J.S. J. Neurosci. Res. (2003) [Pubmed]
  5. Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea. Hossain, W.A., Antic, S.D., Yang, Y., Rasband, M.N., Morest, D.K. J. Neurosci. (2005) [Pubmed]
  6. Activation events during thymic selection. Bendelac, A., Matzinger, P., Seder, R.A., Paul, W.E., Schwartz, R.H. J. Exp. Med. (1992) [Pubmed]
  7. Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice. Raman, I.M., Sprunger, L.K., Meisler, M.H., Bean, B.P. Neuron (1997) [Pubmed]
  8. Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3. Sprunger, L.K., Escayg, A., Tallaksen-Greene, S., Albin, R.L., Meisler, M.H. Hum. Mol. Genet. (1999) [Pubmed]
  9. Pathological and genetic analysis of the degenerating muscle (dmu) mouse: a new allele of Scn8a. De Repentigny, Y., Côté, P.D., Pool, M., Bernier, G., Girard, S., Vidal, S.M., Kothary, R. Hum. Mol. Genet. (2001) [Pubmed]
  10. Three ENU-induced neurological mutations in the pore loop of sodium channel Scn8a (Na(v)1.6) and a genetically linked retinal mutation, rd13. Buchner, D.A., Seburn, K.L., Frankel, W.N., Meisler, M.H. Mamm. Genome (2004) [Pubmed]
  11. The contribution of resurgent sodium current to high-frequency firing in Purkinje neurons: an experimental and modeling study. Khaliq, Z.M., Gouwens, N.W., Raman, I.M. J. Neurosci. (2003) [Pubmed]
  12. A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting. Kohrman, D.C., Smith, M.R., Goldin, A.L., Harris, J., Meisler, M.H. J. Neurosci. (1996) [Pubmed]
  13. Functional analysis of the mouse Scn8a sodium channel. Smith, M.R., Smith, R.D., Plummer, N.W., Meisler, M.H., Goldin, A.L. J. Neurosci. (1998) [Pubmed]
  14. Reduced spontaneous activity in the dorsal cochlear nucleus of Scn8a mutant mice. Chen, K., Sprunger, L.K., Meisler, M.H., Waller, H.J., Godfrey, D.A. Brain Res. (1999) [Pubmed]
  15. Expression of Nav1.6 sodium channels by Schwann cells at neuromuscular junctions: role in the motor endplate disease phenotype. Musarella, M., Alcaraz, G., Caillol, G., Boudier, J.L., Couraud, F., Autillo-Touati, A. Glia (2006) [Pubmed]
  16. Mutation detection in the med and medJ alleles of the sodium channel Scn8a. Unusual splicing due to a minor class AT-AC intron. Kohrman, D.C., Harris, J.B., Meisler, M.H. J. Biol. Chem. (1996) [Pubmed]
  17. A mutation that causes ataxia shifts the voltage-dependence of the Scn8a sodium channel. Smith, M.R., Goldin, A.L. Neuroreport (1999) [Pubmed]
  18. Paranodal axoglial junction is required for the maintenance of the Nav1.6-type sodium channel in the node of Ranvier in the optic nerves but not in peripheral nerve fibers in the sulfatide-deficient mice. Suzuki, A., Hoshi, T., Ishibashi, T., Hayashi, A., Yamaguchi, Y., Baba, H. Glia (2004) [Pubmed]
  19. A comparative electrophysiological study of motor end-plate diseased skeletal muscle in the mouse. Weinstein, S.P. J. Physiol. (Lond.) (1980) [Pubmed]
  20. Is resurgent Na+ current an alpha-subunit-specific property? Maybe not. Focus on "Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice". Colbert, C.M. J. Neurophysiol. (2004) [Pubmed]
  21. Isolation, characterization and inactivation of the mouse Mgat3 gene: the bisecting N-acetylglucosamine in asparagine-linked oligosaccharides appears dispensable for viability and reproduction. Priatel, J.J., Sarkar, M., Schachter, H., Marth, J.D. Glycobiology (1997) [Pubmed]
  22. Calcium-binding protein, parvalbumin, is reduced in mutant mammalian muscle with abnormal contractile properties. Stuhlfauth, I., Reininghaus, J., Jockusch, H., Heizmann, C.W. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  23. Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15. Kohrman, D.C., Plummer, N.W., Schuster, T., Jones, J.M., Jang, W., Burgess, D.L., Galt, J., Spear, B.T., Meisler, M.H. Genomics (1995) [Pubmed]
  24. The neuronal voltage-gated sodium channel, Scn8a, is essential for postnatal maturation of spinal, but not oculomotor, motor units. Porter, J.D., Goldstein, L.A., Kasarskis, E.J., Brueckner, J.K., Spear, B.T. Exp. Neurol. (1996) [Pubmed]
  25. Nerve transplantation shows that motor end-plate disease is not a primary Schwann cell defect. Füchtbauer, E.M. Exp. Neurol. (1987) [Pubmed]
  26. Developmental and regional expression of sodium channel isoform NaCh6 in the rat central nervous system. Schaller, K.L., Caldwell, J.H. J. Comp. Neurol. (2000) [Pubmed]
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