NER rat strain: a new type of genetic model in epilepsy research.
OBJECTIVE
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.
Noda
A
A
Research Institute for Animal Science in Biochemistry and Toxicology, Kanagawa, Japan.
Hashizume
R
R
Maihara
T
T
Tomizawa
Y
Y
Ito
Y
Y
Inoue
M
M
Kobayashi
K
K
Asano
Y
Y
Sasa
M
M
Serikawa
T
T
D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D005808:Genes, Recessive; D007178:Inbreeding; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics*; D017208:Rats, Wistar / Q000235:genetics; D014743:Videotape Recording