High-resolution mapping of the sodium channel modifier Scnm1 on mouse chromosome 3 and identification of a 1.3-kb recombination hot spot

Genomics. 2003 Oct;82(4):452-9. doi: 10.1016/s0888-7543(03)00152-6.


Variation between inbred strains of mice can be used to identify modifier genes affecting the susceptibility to inherited disease. The medJ allele of the sodium channel Scn8a contains a splice site mutation that results in sodium channel deficiency. The severity of the neurological disorder is determined by the modifier locus Scnm1. The wild-type allele of the modifier results in correct splicing of 10% of Scn8amedJ pre-mRNA and a dystonic phenotype. The susceptible allele of the modifier in strain C57BL/6J results in 5% correctly spliced transcripts and a lethal phenotype. A mapping cross with C3H using 26 new markers and 2304 affected F2 animals localized the modifier gene to a 950-kb interval on mouse chromosome 3. Fine mapping of recombination breakpoints revealed a recombination hot spot of 1.3 kb. The ratio of genetic to physical distance in the hot spot is 85 cM/Mb, two orders of magnitude higher than the mouse genome average of 0.5 cM/Mb. The role of the modifier in other disorders in human and mouse can be tested with linked markers described here.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • Chromosome Mapping / methods*
  • Crosses, Genetic
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neuromuscular Diseases / genetics
  • RNA Splicing Factors
  • Sequence Analysis, DNA
  • Sodium Channels / genetics*


  • Carrier Proteins
  • Genetic Markers
  • RNA Splicing Factors
  • SCNM1 protein, human
  • Scnm1 protein, mouse
  • Sodium Channels