Modeling Human Epilepsies in Mice


  • Jeffrey L. Noebels

    1. Blue Bird Circle Developmental Neurogenetics Laboratory, Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.
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Address correspondence and reprint requests to Dr. J. L. Noebels at Department of Neurology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, U.S.A. E-mail:


Summary: Two categories of mouse models of human epilepsy are now contributing to the experimental analysis of inherited seizure disorders. The first type includes homologous genetic models arrived at in the classic way; the genes from human inherited epilepsy syndromes are cloned, and mice are recreated with functionally identical mutations. The second category involves the reverse strategy: mutating single genes in mice and determining whether the newly created nervous system develops epilepsy. These “gene-forward” models define specific candidate genes that can then be tested for possible involvement in human epilepsies. Spontaneous mutation of genes in mice and other species is also a source for candidate genes. As each of these genes and their physiologic functions is defined, the focus can shift to (a) fully characterizing the clinical epilepsy phenotype, (b) tracing the steps in the molecular pathogenesis of the disorder, and (c) pinpointing molecular targets for early intervention. Along with providing a unique opportunity to understand the mechanisms of inherited epileptogenesis, the mouse models serve as ideal biological test systems to search for novel therapeutic strategies.