|Budget Amount *help
¥6,500,000 (Direct Cost : ¥6,500,000)
Fiscal Year 1997 : ¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1996 : ¥4,100,000 (Direct Cost : ¥4,100,000)
We characterized and evaluated as an animal model of epilepsy NER,a new epileptic rat strain, which was developed by inbreeding rats with spontaneous tonic-clonic seizures in a stock of Crj : Wistar. After the F9 generation, 94%-98% of NER exhibited spontaneous tonic-clonic convulsions, beginning with neck and forelimb clonus, wild jumping/running, opisthotonic posturing, and evolving to tonic, then clonic convulsion, followed by postictal flaccidity. Most seizure onsets occurred between 2-4 months of age, and the incidence was 0.45ア0.21 seizures in 12h. Ictal cortical and hippocampal EEGs were characterized by high-voltage spikes followed by diffuse spike-and wave or polyspike-and-wave complexes. NER revealed seizure susceptibility to pentylenetetrazol, tossing, and transcorneal electroshock. Mating experiments revealed that 0% (0/46) of the animals in F1,25.5% (13/51) in F2, and 63.6% (56/88) in backcross progenies exhibited spontaneous convulsions without sex difference. For all epileptic traits, no pathologic changes were demonstrated in the CNS.In order to confirm the mode of inheritance and locate the causative gene for epilepsy on the rat genome, we developed backcross progeny of NER with a seizure-resistant strain F344/DuCrj rats. The seizure propensity was specified by giving tossing stimuli. Linkage anaysis was made with whole genome scanning, and a significant association was found at D3M2Mit382 on chromosome 3. The spontaneous convulsions are comparable to generalized tonic-clonic seizures in human, and NER can serve as a new genetic model in epilepsy research.