Mammalian Genome

, Volume 18, Issue 1, pp 23–31

Use of chromosome substitution strains to identify seizure susceptibility loci in mice

  • Melodie R. Winawer
  • Rachel Kuperman
  • Martin Niethammer
  • Steven Sherman
  • Daniel Rabinowitz
  • Irene Plana Guell
  • Christine A. Ponder
  • Abraham A. Palmer
Article

DOI: 10.1007/s00335-006-0087-6

Cite this article as:
Winawer, M.R., Kuperman, R., Niethammer, M. et al. Mamm Genome (2007) 18: 23. doi:10.1007/s00335-006-0087-6

Abstract

Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) × A/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Melodie R. Winawer
    • 1
  • Rachel Kuperman
    • 2
  • Martin Niethammer
    • 1
  • Steven Sherman
    • 3
  • Daniel Rabinowitz
    • 4
  • Irene Plana Guell
    • 4
  • Christine A. Ponder
    • 5
  • Abraham A. Palmer
    • 6
  1. 1.Department of NeurologyColumbia UniversityNew YorkUSA
  2. 2.Department of Pediatric NeurologyColumbia UniversityNew YorkUSA
  3. 3.Department of EpidemiologyMailman School of Public Health, Columbia UniversityNew YorkUSA
  4. 4.Department of StatisticsColumbia UniversityNew YorkUSA
  5. 5.Department of Genetics and DevelopmentColumbia UniversityNew YorkUSA
  6. 6.Department of Human GeneticsUniversity of ChicagoChicagoUSA
  7. 7.Department of NeurologyColumbia University, GH Sergievsky CenterNew YorkUSA