Mammalian Genome

, Volume 15, Issue 9, pp 698–703

Genetic and phenotypic analysis of seizure susceptibility in PL/J mice

  • Toshimori Kitami
  • Sheila Ernest
  • Laura Gallaugher
  • Lee Friedman
  • Wayne N. Frankel
  • Joseph H. Nadeau
Article

DOI: 10.1007/s00335-004-3007-7

Cite this article as:
Kitami, T., Ernest, S., Gallaugher, L. et al. Mamm Genome (2004) 15: 698. doi:10.1007/s00335-004-3007-7

Abstract

Epilepsy is one of the most common but genetically complex neurological disorders in humans. Identifying animal models that recapitulate human epilepsies is important for pharmacological studies of anticonvulsants, dissection of molecular and biochemical pathogenesis of epilepsy, and discovery of epilepsy susceptibility genes. We discovered that the PL/J inbred mouse strain is susceptible to handling- and rhythmic tossing–induced seizure. The tonic–clonic and generalized seizures observed after induction were accompanied by abnormal EEGs, similar to seizures observed in EL and SWXL-4 mice. PL/J mice also had an extremely low threshold to electroconvulsive seizures compared to other strains and showed variable sensitivity to pentylenetetrazole-induced seizures. Gross neurostructural abnormalities were not found in PL/J mice. Crosses with the seizure-resistant C57BL/6 J strain revealed semidominant inheritance of the rhythmic tossing seizure trait with low penetrance. F2 progeny indicated that the genetic inheritance of seizure susceptibility in PL/J is non-Mendelian. We crossed DBA/2 J mice, which are resistant to rhythmic tossing seizure but susceptible to audiogenic seizures, to PL/J. We found that seizure penetrance in (DBA/2 J × PL/J)F1 mice was similar to the penetrance in (C57BL/6 J × PL/J)F1 mice but the severity and frequency of seizure were higher in (DBA/2 J × PL/J)F1 mice. The PL/J strain serves as an interesting new model for studying the genetics, neurobiology, and pharmacology of epilepsy.

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Toshimori Kitami
    • 1
  • Sheila Ernest
    • 1
  • Laura Gallaugher
    • 2
  • Lee Friedman
    • 3
  • Wayne N. Frankel
    • 4
  • Joseph H. Nadeau
    • 1
    • 5
  1. 1.Department of Genetics, Case Western Reserve University School of MedicineClevelandUSA
  2. 2.Research ServiceLouis Stokes DVA Medical CenterClevelandUSA
  3. 3.The Mental Illness and Neuroscience Discovery Institute (MIND)AlbuquerqueUSA
  4. 4.The Jackson LaboratoryBar HarborUSA
  5. 5.Center for Human GeneticsUniversity Hospitals of ClevelandClevelandUSA