STRAIN INFORMATION
Family Identifier
 NMF5
Synonym(s)
 Scn8anmf5; Scn8a5J; C57BL/6J-Scn8a5J/J; JR#4105
Synopsis
 Early onset bilateral hind limb paralysis; the mutants are small, have a thin retina.
Gene Symbol
 Scn8a (View MGI Record)
Gene
 Sodium channel, voltage-gated, type VIII, alpha polypeptide
Allele Symbol
 Scn8anmf5 (View MGI Record)
Allele
 neuroscience mutagenesis facility5
Abnormal Assay(s)
 Assay: Overt movement/posture

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

Assay: Body weight

   Domain(s): Growth/Development

Assay: Eye histology

   Domain(s): Histology
Phenotype Description
 Mice develop bilateral hind limb paralysis between 14-22 days (average onset 16.9 +/- 2.1 days) followed by death between 3-4 weeks of age. Mutants of either gender have been produced. Homozygotes are not viable so that a colony has to be maintained through heterozygote matings and ovarian transplants. A complementation test between NMF5 and C3HeB/FeJ-Scn8amed-J (JR#3798) revealed that the motor phenotype of NMF5 represents a new allele of Scn8a, which encodes a type VIII voltage-gated sodium channel alpha polypeptide. Affected mice were found in each of 3 litters from heterozygote matings (NMF5 x Scn8amed-J). Of the 25 mice born, 28% were affected (4/8, 1/9, 2/8, litters 1-3, respectively). Additional complementation tests showed NMF5 to be an allele of NMF58, and recent sequencing data confirmed the allelic relationship of NMF58 and Scn8a, and therefore of NMF5 and Scn8a (Mammalian Genome, 15,4, 2004). However, we note that the retinal phenotype detected in NMF5 has not been reported for any Scn8a allele. To determine whether the retinal phenotype was caused by a closely-linked but independent recessive mutation, we attempted to separate the two mutations by genetic recombinantion. Nineteen F2 intercross progeny from C57BL/6J-Scn8anmf5 and A.B6-Tyr+ mice were genotyped for Scn8a and two flanking markers, D15Mit43 and D15Mit246, to detect mice carrying recombinant chromosomes in the Scn8a region. Individual recombinants were subsequently analyzed histologically. Although the two phenotypes were concordant in an Scn8anmf5/+ mouse carrying a recombination event between D15Mit43 and Scn8a, the retinal layer defect was detected in a mouse carrying a recombination event between Scn8a (heterozygous) and the telomeric marker D15Mit246 (homozygous B6-Scn8anmf5-like). These data suggest that the retinal phenotype is caused by a recessive mutation that maps approximately 3.0cM telomeric to Scn8a.
Pathology Report
 Standard pathology work-up on 6 mutants and 2 unaffected mice (12-40 days of age) showed no apparent defects in PNS or muscle. The ventricles of the brain were enlarged; mild hydrocephalus was observed in 7 of 8 mice examined. A paucity of granule cells was observed in small areas of the cerebellum. Additional muscle histology showed no evidence of atrophy, regeneration or abnormalities in the neuromuscular junction. The outer layer of the retina was thin, consisting of 6-7 rather than the expected 11 cell layers in all 8 mice.
HERITABILITY AND MAPPING INFORMATION
Background Strain
 C57BL/6J
Heritability Mode
 Recessive
Heritability Status
 Proven; 3 heterozygote matings produced 7 affected mice in a total of 28 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. (27) NMF5 have been requested by and distributed to 7 investigators.
Contact e-Mail Address
 nmf-mice@jax.org