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.: Home > Animal Bioresource in Japan > 2015 > Volume 64 Number 1 > Tadao SERIKAWA, Tomoji MASHIMO, Takashi KURAMORO, Birger VOIGT, Yukihiro OHNO, Masashi SASA

Advances on genetic rat models of epilepsy

Tadao SERIKAWA, Tomoji MASHIMO, Takashi KURAMORO, Birger VOIGT, Yukihiro OHNO, Masashi SASA
1)Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan 2)Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka 569-1094, Japan 3)Nagisa clinic, Hirakata, Osaka 573-1183, Japan
Abstract :

Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

Keywords :
antiepileptic drug (AED), ENU mutagenesis, epileptic rat model, epileptogenesis, spontaneous mutation

Date Deposited : 07 Apr 2015 16:16

Last Modified : 07 Apr 2015 16:16

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Volume 64, Number 1, - 2015

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