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Identification of a monogenic locus (jams1) causing juvenile audiogenic seizures in mice.

Epilepsy is a debilitating disease with a strong genetic component. Positional cloning has identified a few genes for rare monogenic epilepsy syndromes; however, the genetics of common human epilepsies are too complex to be analyzed easily by current techniques. Mouse models of epilepsy can further this analysis by eliminating genetic background heterogeneity and enabling the production of sufficient numbers of offspring. Here, we report that Black Swiss mice have a heretofore unrecognized specific susceptibility to audiogenic seizures. These seizures are characterized by wild running, loss of righting reflex, and tonic flexion and extension, and are followed by a postictal period. The susceptibility to these seizures is developmentally regulated, peaking at 21 d of age and nearly disappearing by adulthood. Interestingly, both the susceptibility to seizures and their developmental regulation appear unrelated to hearing thresholds in the Black Swiss strain and backcrossed progeny. Genetic mapping and linkage analysis of hybrid mice localize the seizure gene, jams1 (juvenile audiogenic monogenic seizures), to a 1.6 +/- 0.5 centimorgan (cM) region on mouse chromosome 10, delimited by the gene basigin (Bsg) and marker D10Mit140. Interestingly, the majority of the critical region is syntenic to a region on human chromosome 19p13.3 implicated in a familial form of juvenile febrile convulsions. Cloning the gene for audiogenic seizures in these mice may provide important insight into the fundamental mechanisms for developmentally regulated human epilepsy syndromes.

Pubmed ID: 12451109


  • Misawa H
  • Sherr EH
  • Lee DJ
  • Chetkovich DM
  • Tan A
  • Schreiner CE
  • Bredt DS


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

December 1, 2002

Associated Grants

  • Agency: NIDCD NIH HHS, Id: R01 DC002260
  • Agency: NIDCD NIH HHS, Id: R01 DC002260-08

Mesh Terms

  • Acoustic Stimulation
  • Age Factors
  • Animals
  • Antigens, CD
  • Antigens, CD147
  • Antigens, Neoplasm
  • Antigens, Surface
  • Auditory Threshold
  • Avian Proteins
  • Blood Proteins
  • Carrier Proteins
  • Disease Models, Animal
  • Epilepsy, Reflex
  • Evoked Potentials, Auditory, Brain Stem
  • Gene Expression Regulation, Developmental
  • Genes, Recessive
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Genotype
  • Hearing Tests
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Microsatellite Repeats
  • N-Methylaspartate
  • Physical Chromosome Mapping
  • Picrotoxin
  • Vesicular Transport Proteins