新しいてんかんモデルラットの開発

自发性癫痫大鼠（SER）是一种双突变体（zi/zi，tm/tm），通过将在西德国SD群体中发现的zitter纯合子大鼠（zi/zi）与在（京都大学医学实验动物研究所）的Kyo：Wistar群体中发现的震颤杂合子大鼠（tm/+）交配获得。在该项目中，我们建立了一个群体的特定病原体自由动物的SER，除了一个菌株的SER保持全同胞交配，并检查了性状，以估计是否SER是一个合适的模型，人类癫痫。主要研究结果如下：1.建立了一个能稳定供应SER的SPF群体.全同胞交配的一个品系达到F10.3。Zitter基因位于连锁群IV上，与Hao-1.4的距离为10 cM。除强直性惊厥外，在SER中还观察到以EEG中5-7 Hz棘波和波群的阵发性出现为特征的失神样发作。在震颤大鼠中也观察到失神样发作。在单次接种抗癫痫药物的实验中，SER和震颤大鼠的癫痫发作被特异性抑制。曲美双酮和乙琥胺可抑制失神样发作，而对强直性惊厥无影响。与此相反，苯妥英钠抑制强直性发作，而不影响失神样发作。苯巴比妥和丙戊酸钠抑制癫痫发作的程度相似。7.研究了持续摄入苯巴比妥对SER的长期影响。强直性惊厥持续受到抑制，直到15周龄，虽然它是不完全的。在给予含0.1%药物的食物颗粒的SER中观察到体重显著增加和存活期延长。本研究对失神样发作无明显影响，因此，SER和震颤大鼠是一种较好的癫痫模型。

The spontaneously epileptic rat (SER) is a double mutant (zi/zi, tm/tm), obtained by mating the zitter homozygous rat (zi/zi), found in an SD colony in West Germany, with the tremor heterozygous rat (tm/+) found in a Kyo:Wistar colony in (Institute of Laboratory Animals, Facutly of Medicine, Kyoto University). In the project, we made a colony of specific pathogen free animals of SER, in addition to a strain of SER maintained by full-sib matings, and examined the traits to estimate whether or not SER is a suitable model of human epilepsy. Results obtained were as follows:1. An SPF colony that can supply SER regularly was made.2. A strain of full-sib matings reached F10.3. Zitter gene was assigned on linkage group IV with a distance of 10 cM from Hao-1.4. In addition to tonic convulstion, absence-like seizures characterized by paroxysmal appearance of 5-7 Hz spike and wave complex in EEG were observed in SER.5. The absence-like seizures were also observed in tremor rats.6. In the test of single inoculation with anti-epileptic drugs, epileptic seizures in SER and tremor rat were specificuly inhibited. The absence-like seizures were inhibited by trimethadione and ethosuximide,while the tonic convulsion was not affected by these drugs. In contrast, phenytoin inhibited the tonic seizures without affecting the absence-like seizures. Phenobarbital and sodium valproate inhibited both seizures to a similar degree.7. The long-term effects of continual intake of phenobarbital on SER were examined. Tonic convulsion was continually inhibited until 15 weeks of age, although it was not complete. Body weight increased markedly and prolonged survival was seen in SER given food pellets containing 0.1 % of the drug. Absence-like seizures were not affected in this study.From the results, we concluded that SER and tremor rat are useful medels for human epilepsy.