NER Rat Strain: A New Type of Genetic Model in Epilepsy Research

• Published in: Epilepsia (Copenhagen) 1998-01, Vol.39 (1), p.99-107
• Main Authors: Noda, Atsushi, Hashizume, Ryoichi, Maihara, Toshiro, Tomizawa, Yasuhiro, Ito, Yoshihiko, Inoue, Maki, Kobayashi, Kinji, Asano, Yuzo, Sasa, Masashi, Serikawa, Tadao
• Format: Article
• Language: English
• Subjects: Animal model; Animals; Biological and medical sciences; Cerebral Cortex - physiopathology; Disease Models, Animal; Electroencephalography; Epilepsy - genetics; Epilepsy - physiopathology; Epilepy; Genes, Recessive; Genetics; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Inbreeding; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Rat; Rats; Rats, Inbred Strains - genetics; Rats, Wistar - genetics; Seizure susceptibility; Videotape Recording
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1157.1998.tb01281.x

Purpose: 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. Methods: Animals were monitored through the inbreeding course, and video‐EEGs were recorded selectively. External seizure‐provoking stimuli were applied to NER and to a control parental strain. F1, F2, and backcross progenies were produced between NER and a nonepileptic unrelated strain. Pathologic study included hematoxylin‐and‐eosin (HE), Klüver‐Barrera's, modified Bodian silver, and neo‐Timm's staining. Results: 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 ± 0.21 seizures in 12 h. 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, but not to tactile, photic, or acoustic stimuli, or to transauricular 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 tonic‐clonic convulsions without sex difference. For all these epileptic traits, no pathologic changes were demonstrated in the CNS. Conclusions: NER frequently exhibited spontaneous convulsions, controlled by a major autosomal recessive gene for epilepsy, that are comparable to generalized tonic‐clonic seizures in humans. This can serve as a new genetic model in epilepsy research.