These mice carry an ENU-induced mutation shown to be a new allele of Scn8a and characterized by functional lose of hind limbs bilaterally.
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The mutants lose function of hind limbs bilaterally between 13-18 days (mean 15.25 +/-.2 days; n=13) and die between 3 and 5 weeks of age.
A series of complementation tests was performed to show that NMF2 is an allele of Scn8a 2 matings between NMF5/+ and NMF2/+ resulted in 2 affected mice in a total of 13 progeny, and since NMF5 has been shown to be an allele of NMF58, NMF2 can also be regarded as an allele of NMF58. Recent sequencing data confirmed the allelic relationship of NMF58 and Scn8a, and therefore also those of NMF2, NMF5, and Scn8a (Mammalian Genome, 15,4, 2004). Standard pathology work-up on 4 mutants (age 18-19 days) showed no muscle atrophy or necrosis. Additional histology of hindlimb muscles showed no evidence of reinnervation/regeneration and normal neuromuscular junction morphology in all mice. One mutant had severe hydrocephaly. Standard eye histology on one mutant and one control littermate (age 16 days) showed no abnormalities. Mutants are small in size.
Mutants of either gender have been produced, however homozygotes are not viable.
This phenotypic deviant was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males (Stock No. 000664), in the Neuroscience Mutagenesis facility at The Jackson Laboratory. Mutagenized males were crossed to C57BL/6J females; G3 descendants of the mutagenized males were selected for neurological impairment.
|Allele Name||4 Jackson|
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||neuroscience mutagenesis facility, 2; NMF2; Scn8anmf2|
|Gene Symbol and Name||Scn8a, sodium channel, voltage-gated, type VIII, alpha|
|Strain of Origin||C57BL/6J|
|Molecular Note||This phenotypic mutant was identified in an ENU mutagenesis screen. A complementation test between nmf2 and Scn8anmf5 revealed that nmf2 is a new allele of Scn8a. Sequence analysis demonstrated that an A-to-C transversion mutation occurred in the coding sequence that is predicted to change asparagine 1370 to threonine. This conserved residue is within the S5-S6 pore loop of transmembrane domain 3.|