Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names C3HeB/FeJ-Scn8amed/J    (Changed: 13-MAR-08 ) Type Congenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N8+N5F12pN1 Generation Definitions

Appearance
agouti, unaffected
Related Genotype: A/A Scn8a^med/+ or A/A +/+

Development
The original Scn8a^med spontaneous mutant allele arose in the multiple recessive PCT Stock at Harwell in 1958 and was initially called "seal" (Searle AG, 1962). The frozen embryo stock of Scn8a^med at the MRC UK Mouse Genome Center at Harwell was on a mixed background that included C3H and 101. John Harris maintained this allele in Newcastle, UK from the early 1970s then passed it off to Miriam Meisler who maintained it by backcrossing to C3HeB/FeJ. The Jackson Laboratory received from Dr. Meisler in March 2000 heterozygous C3HeB/FeJ-Scn8a^med males at N7. Since then, this strain has been bred to C3HeB/FeJ at each generation.

Control Information

	Control
	Wild-type from the colony
	000658 C3HeB/FeJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Scn8a

012945	B6(C3Fe)-Scn8a8J/Frk
003799	B6.D2-Scn8amed-jo/J
005463	B6;CByJ-Scn8a7J/J
000304	B6C3Fe a/a-Krt71Ca Scn8amed-J/J
012946	C3Fe.B6-Scn8a8J/Frk
004102	C57BL/6J-Scn8a4J/J
004105	C57BL/6J-Scn8a5J/J

View Strains carrying other alleles of Scn8a     (7 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Cognitive Impairment with or without Cerebellar Ataxia; CIAT   (SCN8A) Epileptic Encephalopathy, Early Infantile, 13; EIEE13   (SCN8A)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Scn8a^med/Scn8a⁺

        C3Fe.Cg-Scn8a^med/J

• behavior/neurological phenotype
• abnormal spike wave discharge
  • mice exhibit spike wave discharge (SWD) accompanied by behavior arrest unlike wild-type mice   (MGI Ref ID J:147199)
  • the average incidence of SWD is higher than in Scn8a^med heterozygotes but lower than in Scn8a^8J heterozygotes   (MGI Ref ID J:147199)
  • ethosuximide treatment results in 11-fold fewer and shorter SWD compared to a 3-fold increase in frequencies following saline treatment   (MGI Ref ID J:147199)
  • the frequency of SWD during slow-wave sleep and paradoxical SWD are higher during the dark cycle than during the light cycle   (MGI Ref ID J:147199)
• decreased susceptibility to pharmacologically induced seizures
  • following exposure to flurothyl, mice exhibit a 25% increase in latency to myoclonic jerk and a 58% increase in latency to generalized tonic-clonic seizure (GTCS) compared to in similarly treated wild-type mice   (MGI Ref ID J:129998)
  • following exposure to kainic acid, mice exhibit reduced seizure severity and no GTCS compared to similarly treated wild-type mice   (MGI Ref ID J:129998)
• nervous system phenotype
• abnormal spike wave discharge
  • mice exhibit spike wave discharge (SWD) accompanied by behavior arrest unlike wild-type mice   (MGI Ref ID J:147199)
  • the average incidence of SWD is higher than in Scn8a^med heterozygotes but lower than in Scn8a^8J heterozygotes   (MGI Ref ID J:147199)
  • ethosuximide treatment results in 11-fold fewer and shorter SWD compared to a 3-fold increase in frequencies following saline treatment   (MGI Ref ID J:147199)
  • the frequency of SWD during slow-wave sleep and paradoxical SWD are higher during the dark cycle than during the light cycle   (MGI Ref ID J:147199)
• decreased susceptibility to pharmacologically induced seizures
  • following exposure to flurothyl, mice exhibit a 25% increase in latency to myoclonic jerk and a 58% increase in latency to generalized tonic-clonic seizure (GTCS) compared to in similarly treated wild-type mice   (MGI Ref ID J:129998)
  • following exposure to kainic acid, mice exhibit reduced seizure severity and no GTCS compared to similarly treated wild-type mice   (MGI Ref ID J:129998)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Scn8a^med/Scn8a^med

        PCT

• mortality/aging
• postnatal lethality
  • mice die within 2 weeks of onset of weakness   (MGI Ref ID J:5153)
  • most mice die by day 19   (MGI Ref ID J:28678)
  • mice die at about 3 weeks of age   (MGI Ref ID J:28679)
• nervous system phenotype
• abnormal action potential
  • intracellular recordings from single muscle fibers show that with longer survival of the animal an increasing proportion of the fibers fail to show end-plate potentials or action potentials in response to nerve stimulation   (MGI Ref ID J:5192)
• abnormal endplate potential
  • intracellular recordings from single muscle fibers show that with longer survival of the animal an increasing proportion of the fibers fail to show end-plate potentials or action potentials in response to nerve stimulation   (MGI Ref ID J:5192)
• abnormal miniature endplate potential
  • the frequency of miniature endplate potentials is increased compared to in wild-type and is not increased by titanic stimulation   (MGI Ref ID J:5192)
• abnormal nerve conduction
  • conduction velocity is slower, the refractory period is prolonged and the temperature sensitivity is higher than in wild-type mice   (MGI Ref ID J:6888)
• abnormal neuromuscular synapse morphology
  • motor nerves show marked terminal sprouting, the sprouts growing beyond the normal confines on the motor end-plates   (MGI Ref ID J:5153)
  • motor end plates become progressively more complex and elongated with fine branching of the nerve fiber within the region of motor terminal   (MGI Ref ID J:28678)
  • mice exhibit defects in neuromuscular transmission   (MGI Ref ID J:28678)
• demyelination
  • the demyelinated gaps of the nodes of Ranvier in the sciatic nerve are wider than in wild-type mice   (MGI Ref ID J:7297)
  • most axons show signs of paranodal demyelination   (MGI Ref ID J:6888)
• muscle phenotype
• abnormal muscle physiology
  • muscles exhibit spontaneous fibrillation in isolated preparations   (MGI Ref ID J:5192)
  • muscles give only a weak twitch or fail to contract in response to nerve stimulation   (MGI Ref ID J:5192)
  • direct stimulation results in a twitch response that is slower than in wild-type muscles   (MGI Ref ID J:5192)
  • however, peripheral nerve conduction is normal   (MGI Ref ID J:5192)
• • abnormal muscle tone
    • at 1 week of age mice are softer and floppier than wild-type mice as if lacking muscle tone   (MGI Ref ID J:28679)
  • progressive muscle weakness
    • mice exhibit progressive weakness of skeletal muscle beginning at 8 to 10 days old   (MGI Ref ID J:5153)
    • beginning at day 9 mice exhibit progressive weakness and wasting of skeletal muscle   (MGI Ref ID J:28678)
• muscular atrophy
  • mice exhibit progressive atrophy of skeletal muscle that is particularly severe in proximal limb muscles   (MGI Ref ID J:5153)
• behavior/neurological phenotype
• hindlimb paralysis
  • mice exhibit progressive hindlimb paralysis   (MGI Ref ID J:28679)
• paraparesis
  • mice become shaky as hindlimb function is lost and develop a seal-like movement with head going up and down   (MGI Ref ID J:28679)

Scn8a^med/Scn8a^med

        involves: C3HeB/FeJ * DBA/2J

• vision/eye phenotype
• abnormal eye electrophysiology
  • at P16, alpha and beta waves are reduced and latency times are increased compared to in wild-type mice   (MGI Ref ID J:98511)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Scn8a^med related

Cell Biology Research
Channel and Transporter Defects
      sodium

Developmental Biology Research
Neurodevelopmental Defects

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency Associated with Other Defects

Neurobiology Research
Ataxia (Movement) Defects
Channel and Transporter Defects
      sodium
Neurodevelopmental Defects
Neuromuscular Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Scn8amed
Allele Name		motor end plate disease
Allele Type		Spontaneous
Common Name(s)		med;
Strain of Origin		PCT
Gene Symbol and Name		Scn8a, sodium channel, voltage-gated, type VIII, alpha
Chromosome		15
Gene Common Name(s)		AI853486; C630029C19Rik; CERIII; CIAT; EIEE13; MED; NMF335; NaCh6; Nav1.6; PN4; RIKEN cDNA C630029C19 gene; ataxia 3; degenerating muscle; dmu; expressed sequence AI853486; med; mnd-2; mnd2; motor end-plate disease; neurological 14; neuroscience mutagenesis facility, 2; neuroscience mutagenesis facility, 335; neuroscience mutagenesis facility, 58; nmf2; nmf335; nmf58; nur14; seal;
Molecular Note		The mutation was identified as a small LINE element insertion into exon 2 of the Scn8a gene. This results in exon skipping which is influenced by the AT-AC splice sites in intron 2, and generates a very short inactive protein. This allele is a predictednull. [MGI Ref ID J:34154]

Genotyping

Genotyping Information

Genotyping Protocols

Scn8a^med, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Khaliq ZM; Gouwens NW; Raman IM. 2003. The contribution of resurgent sodium current to high-frequency firing in Purkinje neurons: an experimental and modeling study. J Neurosci 23(12):4899-912. [PubMed: 12832512]  [MGI Ref ID J:84325]

Kohrman DC; Harris JB; Meisler MH. 1996. Mutation detection in the med and medJ alleles of the sodium channel Scn8a. Unusual splicing due to a minor class AT-AC intron. J Biol Chem 271(29):17576-81. [PubMed: 8663325]  [MGI Ref ID J:34154]

Scn8a^med related

Aman TK; Raman IM. 2007. Subunit dependence of Na channel slow inactivation and open channel block in cerebellar neurons. Biophys J 92(6):1938-51. [PubMed: 17189307]  [MGI Ref ID J:135625]

Angaut-Petit D; McArdle JJ; Mallart A; Bournaud R; Pincon-Raymond M; Rieger F. 1982. Electrophysiological and morphological studies of a motor nerve in 'motor endplate disease' of the mouse. Proc R Soc Lond B Biol Sci 215(1198):117-25. [PubMed: 6127695]  [MGI Ref ID J:6888]

Bakalian A; Kopmels B; Messer A; Fradelizi D; Delhaye-Bouchaud N; Wollman E; Mariani J. 1992. Peripheral macrophage abnormalities in mutant mice with spinocerebellar degeneration. Res Immunol 143(1):129-39. [PubMed: 1565842]  [MGI Ref ID J:2228]

Black JA; Liu S; Waxman SG. 2009. Sodium channel activity modulates multiple functions in microglia. Glia 57(10):1072-81. [PubMed: 19115387]  [MGI Ref ID J:156207]

Burgess DL; Kohrman DC; Galt J; Plummer NW; Jones JM; Spear B; Meisler MH. 1995. Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'. Nat Genet 10(4):461-5. [PubMed: 7670495]  [MGI Ref ID J:27739]

Carrithers MD; Chatterjee G; Carrithers LM; Offoha R; Iheagwara U; Rahner C; Graham M; Waxman SG. 2009. Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A. J Biol Chem 284(12):8114-26. [PubMed: 19136557]  [MGI Ref ID J:148621]

Cote PD; De Repentigny Y; Coupland SG; Schwab Y; Roux MJ; Levinson SR; Kothary R. 2005. Physiological maturation of photoreceptors depends on the voltage-gated sodium channel NaV1.6 (Scn8a). J Neurosci 25(20):5046-50. [PubMed: 15901786]  [MGI Ref ID J:98511]

De Repentigny Y; Cote PD; Pool M; Bernier G; Girard S; Vidal SM; Kothary R. 2001. Pathological and genetic analysis of the degenerating muscle (dmu) mouse: a new allele of Scn8a. Hum Mol Genet 10(17):1819-27. [PubMed: 11532991]  [MGI Ref ID J:71615]

Dick DJ; Boakes RJ; Harris JB. 1985. A cerebellar abnormality in the mouse with motor end-plate disease. Neuropathol Appl Neurobiol 11(2):141-7. [PubMed: 4022259]  [MGI Ref ID J:7959]

Do MT; Bean BP. 2004. Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice. J Neurophysiol 92(2):726-33. [PubMed: 15056687]  [MGI Ref ID J:102164]

Duchen LW. 1970. Hereditary motor end-plate disease in the mouse: light and electron microscopic studies. J Neurol Neurosurg Psychiatry 33(2):238-50. [PubMed: 4315332]  [MGI Ref ID J:5153]

Duchen LW; Stefani E. 1971. Electrophysiological studies of neuromuscular transmission in hereditary 'motor end-plate disease' of the mouse. J Physiol 212(2):535-48. [PubMed: 4323310]  [MGI Ref ID J:5192]

Duchen LW; Strich SJ. 1966. Motor end-plate disease (med) Mouse News Lett 35:36.  [MGI Ref ID J:28678]

Enomoto A; Han JM; Hsiao CF; Chandler SH. 2007. Sodium currents in mesencephalic trigeminal neurons from Nav1.6 null mice. J Neurophysiol 98(2):710-9. [PubMed: 17522178]  [MGI Ref ID J:147692]

Fuchtbauer EM. 1987. Nerve transplantation shows that motor end-plate disease is not a primary Schwann cell defect. Exp Neurol 97(1):135-42. [PubMed: 3582558]  [MGI Ref ID J:28677]

Grieco TM; Afshari FS; Raman IM. 2002. A role for phosphorylation in the maintenance of resurgent sodium current in cerebellar purkinje neurons. J Neurosci 22(8):3100-7. [PubMed: 11943813]  [MGI Ref ID J:125676]

Harris JB; Boakes RJ; Court JA. 1992. Physiological and biochemical studies on the cerebellar cortex of the murine mutants jolting and motor end-plate disease. J Neurol Sci 110(1-2):186-94. [PubMed: 1506858]  [MGI Ref ID J:1414]

Khaliq ZM; Gouwens NW; Raman IM. 2003. The contribution of resurgent sodium current to high-frequency firing in Purkinje neurons: an experimental and modeling study. J Neurosci 23(12):4899-912. [PubMed: 12832512]  [MGI Ref ID J:84325]

Kohrman DC; Harris JB; Meisler MH. 1996. Mutation detection in the med and medJ alleles of the sodium channel Scn8a. Unusual splicing due to a minor class AT-AC intron. J Biol Chem 271(29):17576-81. [PubMed: 8663325]  [MGI Ref ID J:34154]

Kopmels B; Wollman EE; Guastavino JM; Delhaye-Bouchaud N; Fradelizi D; Mariani J. 1990. Interleukin-1 hyperproduction by in vitro activated peripheral macrophages from cerebellar mutant mice. J Neurochem 55(6):1980-5. [PubMed: 2230805]  [MGI Ref ID J:28095]

Martin MS; Tang B; Papale LA; Yu FH; Catterall WA; Escayg A. 2007. The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy. Hum Mol Genet 16(23):2892-9. [PubMed: 17881658]  [MGI Ref ID J:129998]

McKinney BC; Chow CY; Meisler MH; Murphy GG. 2008. Exaggerated emotional behavior in mice heterozygous null for the sodium channel Scn8a (Nav1.6). Genes Brain Behav 7(6):629-38. [PubMed: 18363861]  [MGI Ref ID J:151158]

Musarella M; Alcaraz G; Caillol G; Boudier JL; Couraud F; Autillo-Touati A. 2006. Expression of Nav1.6 sodium channels by Schwann cells at neuromuscular junctions: role in the motor endplate disease phenotype. Glia 53(1):13-23. [PubMed: 16078241]  [MGI Ref ID J:156150]

Osorio N; Cathala L; Meisler MH; Crest M; Magistretti J; Delmas P. 2010. Persistent Nav1.6 current at axon initial segments tunes spike timing of cerebellar granule cells. J Physiol 588(Pt 4):651-70. [PubMed: 20173079]  [MGI Ref ID J:176774]

Papale LA; Beyer B; Jones JM; Sharkey LM; Tufik S; Epstein M; Letts VA; Meisler MH; Frankel WN; Escayg A. 2009. Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice. Hum Mol Genet 18(9):1633-41. [PubMed: 19254928]  [MGI Ref ID J:147199]

Rieger F; Pincon-Raymond M; Lombet A; Ponzio G; Lazdunski M; Sidman RL. 1984. Paranodal dysmyelination and increase in tetrodotoxin binding sites in the sciatic nerve of the motor end-plate disease (med/med) mouse during postnatal development. Dev Biol 101(2):401-9. [PubMed: 6319212]  [MGI Ref ID J:7297]

Searle AG. 1962. Provisional 'seal' (med) Mouse News Lett 27:34-5.  [MGI Ref ID J:28679]

Searle AG. 1966. Provisional 'seal' re-named 'motor endplate disease' (med) Mouse News Lett 35:28.  [MGI Ref ID J:28680]

Sittl R; Lampert A; Huth T; Schuy ET; Link AS; Fleckenstein J; Alzheimer C; Grafe P; Carr RW. 2012. Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype NaV1.6-resurgent and persistent current. Proc Natl Acad Sci U S A 109(17):6704-9. [PubMed: 22493249]  [MGI Ref ID J:183840]

Stuhlfauth I; Reininghaus J; Jockusch H; Heizmann CW. 1984. Calcium-binding protein, parvalbumin, is reduced in mutant mammalian muscle with abnormal contractile properties. Proc Natl Acad Sci U S A 81(15):4814-8. [PubMed: 6589628]  [MGI Ref ID J:7524]

Swensen AM; Bean BP. 2005. Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance. J Neurosci 25(14):3509-20. [PubMed: 15814781]  [MGI Ref ID J:98597]

Zacks SI; Sheff MF. 1977. Regeneration and differentiation of minced anterior tibial muscle explants from mice with MED myopathy. Lab Invest 36(3):303-9. [PubMed: 839740]  [MGI Ref ID J:5780]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• View the complete collection of spontaneous mutants in the Mouse Mutant Resource.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000658 C3HeB/FeJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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JAX^® Mice, Products & Services Conditions of Use

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