C3Fe.Cg-Scn8a^med/J

Stock number: 003798
Product name: med
Research areas: Cell Biology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research

Description

The mouse neurological mutant 'motor endplate disease' (Scn8a^med) is characterized by early onset progressive paralysis of the hind limbs, severe muscle atrophy, degeneration of Purkinje cells and juvenile lethality.

Detailed description

These mice carry a spontaneous, autosomal recessive mutation characterized by early onset progressive paralysis of the hind limbs, severe muscle atrophy, degeneration of Purkinje cells and juvenile lethality. Mutant mice die 21-23 days after birth having exhibited neurobiological abnormalities of nerve terminal sprouting and swelling and neurotransmission failures. The nonmyelinated gaps of the nodes of Ranvier are significantly widened in mutants compared to control littermates, even in the preclinical stage, although the nodes of Ranvier are not yet ultrastructurally mature. Na+ channels, which are known to be located mainly at the nodes of Ranvier in normal myelinated axons, are increased in number in mutant mice even before the disease becomes clinically established. Both the ultrastructural and biochemical developmental abnormalities of the node of Ranvier rapidly approach their maximal expression as the behavioral signs develop.

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 was bred to C3HeB/FeJ at each generation, and cryopreserved at generation N8+N5F12pN1.

Allele

Symbol: Scn8a^med
Name: motor end plate disease
MGI accession ID: MGI:1856078
Generation method: Spontaneous
Attributes: Null/Knockout
Synonyms: med
Marker symbol: Scn8a
Marker name: sodium channel, voltage-gated, type VIII, alpha
Marker synonyms: ataxia 3; BFIS5; C630029C19Rik; CERIII; CIAT; DEE13; EIEE13; med; mnd2; mnd-2; motor end-plate disease; MYOCL2; NaCh6; Nav1.6; nmf2; nmf335; nmf58; nur14; PN4; seal
Chromosome: 15
Strain of origin: PCT
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 predicted null.