STRAIN INFORMATION
Family Identifier
 NMF58
Synonym(s)
 Scn8anmf58; Scn8a6J; C57BL/6J-Scn8a6J/J; JR#4409
Synopsis
 Seal-like gait; the mutants are small with severely impaired gait.
Gene Symbol
 Scn8a (View MGI Record)
Gene
 Sodium channel, voltage-gated, type VIII, alpha polypeptide
Allele Symbol
 Scn8anmf58 (View MGI Record)
Allele
 neuroscience mutagenesis facility58
Abnormal Assay(s)
 Assay: Overt movement/posture

   Domain(s): Visible Mutants ; Movement/Neuromuscular Function

Assay: Body weight

   Domain(s): Growth/Development
Phenotype Description
 The abnormal gait pattern appears between two and four weeks of age (average age of onset 20.25 +/-2.9 days), and mice move around with difficulty; they also show intense body tremor. The mutants are small, i.e. two of three mutants had significantly lower body weights. Mutants of either gender have been produced; homozygotes are not viable. Because of the map location and the similar, albeit milder phenotype, complementation testing was performed to determine if NMF58 represents an allele of Scn8a; one mating between NMF5/+ (shown to be an allele of Scn8a) and NMF58/+ resulted in 1 affected mouse in a total of 6 progeny, confirming that NMF58 represents an allele of Scn8a. Furthermore, Buchner et al. (Mammalian Genome, 15,4, 2004) have demonstrated that the NMF58 mutation is due to a missense mutations in exon 19 of the Scn8a gene, located to residues in the pore loop of domain 3 of the protein.
Pathology Report
 Standard pathology work-up on one mutant (45 days of age) showed extensive atrophy of muscle fibers of the hind limb. Central nuclei and rowing of the nuclei in longitudinal sections were also observed. Serial spinal cord sections on this and three other mutants (28, 32, or 63 days of age) revealed no abnormalities of motor neurons, spinal roots or nerves. Whole muscle mounts of the hind limb stained with fluorescent-labeled bungarotoxin and SMI 31 revealed no abnormalities of neuromuscular junctions; Bodian stained sciatic nerves appeared normal. Standard eye histology on one mutant (age 24 days) revealed no abnormalities.
HERITABILITY AND MAPPING INFORMATION
Background Strain
 C57BL/6J
Heritability Mode
 Recessive
Heritability Status
 Proven; 2 heterozygote matings produced 6 affected mice in a total of 25 progeny.
Chromosome
 15
Molecular Interval
 see Scn8a
Map
STATUS INFORMATION
Mutant Status
 Cryopreserved Embryos
Comments
 Please note: The majority of frozen NMF embryos is obtained through matings between homozygous (or heterozygous) mutant males and wild-type females; if recovery of mutants is requested, the mice will be shipped as soon as possible following wean without further phenotype or genotype testing. NMF embryos are supplied subject to the General Terms and Conditions of Sale posted at www.jaxmice.jax.org. For prices or further information, please inquire at srp@jax.org or nmf-mice@jax.org. (23) NMF58 have been requested by and distributed to 3 investigators.
Contact e-Mail Address
 nmf-mice@jax.org