Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability

Y. Eugene Yu, Lei Wen, Jeane Silva, Zhongyou Li, Karen Head, Khalid Sossey-Alaoui, Annie Pao, Lin Mei, John K. Cowell

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

LGI1 in humans is responsible for a predisposition to autosomal dominant partial epilepsy with auditory features (ADPEAF). However, mechanisms of how LGI1 mutations cause epilepsy remain unclear. We have used a mouse chromosome engineering strategy to create a null mutation for the gene ortholog encoding LGI1. The Lgi1 null mutant mice show no gross overall developmental abnormalities from routine histopathological analysis. After 12-18 days of age, the homozygous mutant mice all exhibit myoclonic seizures accompanied by rapid jumping and running and die shortly thereafter. The heterozygous mutant mice do not develop seizures. Electrophysiological analysis demonstrates an enhanced excitatory synaptic transmission by increasing the release of the excitatory neurotransmitter glutamate, suggesting a basis for the seizure phenotype. This mouse model, therefore, provides novel insights into the mechanism behind ADPEAF and offers a new opportunity to study the mechanism behind the role of LGI1 in susceptibility to myoclonic seizures.

Original languageEnglish (US)
Article numberddq047
Pages (from-to)1702-1711
Number of pages10
JournalHuman Molecular Genetics
Volume19
Issue number9
DOIs
StatePublished - Feb 3 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Yu, Y. E., Wen, L., Silva, J., Li, Z., Head, K., Sossey-Alaoui, K., Pao, A., Mei, L., & Cowell, J. K. (2010). Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability. Human Molecular Genetics, 19(9), 1702-1711. [ddq047]. https://doi.org/10.1093/hmg/ddq047