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），由在西德SD群体中发现的zitter纯合子大鼠（zi/zi）与在京都大学医学院实验动物研究所Kyo:Wistar群体中发现的震颤杂合子大鼠（tm/+）交配获得。在这个项目中，我们制作了一群特定的无病原体的SER动物，以及一个由全同胞交配维持的SER菌株，并检查了SER的性状，以估计SER是否适合作为人类癫痫的模型。实验结果如下：1。制备了一个能定期供应SER的SPF菌落。一个全同胞交配的菌株达到了F10.3。Zitter基因定位在连锁组IV上，与Hao-1.4的距离为10 cM。除强直性惊厥外，ser还观察到以5- 7hz脑电图峰和波复波的阵发性表现为特征的缺席样癫痫发作。在震颤大鼠中也观察到失神样癫痫发作。单次接种抗癫痫药物可特异性抑制SER和震颤大鼠的癫痫发作。甲美二酮和乙磺酰亚胺对缺席样癫痫发作有抑制作用，对强直性惊厥无影响。相反，苯妥英抑制强直性癫痫发作，但不影响缺席样癫痫发作。苯巴比妥和丙戊酸钠对两种癫痫发作的抑制程度相似。研究了持续服用苯巴比妥对SER的长期影响。强直性惊厥一直被抑制到15周龄，尽管不完全。给予含有0.1%药物的食物颗粒的SER体重明显增加，生存时间延长。在这项研究中，缺席样癫痫发作没有受到影响。结果表明，SER和震颤大鼠是人类癫痫的有效模型。

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.