| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1986: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
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.
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