A Review of Mouse Mutants as Genetic Models of Epilepsy

Seyfried, Thomas N.; Glaser, Gilbert H.

doi:10.1111/j.1528-1157.1985.tb05398.x

Cited by 168 publications

(52 citation statements)

References 71 publications

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“…Spontaneous seizures in particular may contribute to understanding the nature of human epilepsy. In fact, some animal models exhibit seizures that correspond to certain types of epileptic seizures in humans, and the effects of antiepileptic drugs (AEDs) have been evaluated reasonably, using these animals (1)(2)(3)(4). At present, only a few rat models which have spontaneous seizures are known: genetically epilepsy-prone rats (GEPR-3 and GEPR-9) (5); WAG/Rij (6); genetic absence-epilepsy rats from Strasbourg (GAERS) (7); a rat mutant with spontaneous limbic-like seizures (8); tremor rats (TRM) (9); and spontaneously epileptic rats (SER) (3,lO).…”

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confidence: 99%

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

Noda¹,

Hashizume

Maihara

et al. 1998

Epilepsia

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Summary: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. FI, F2, and backcross progenies were produced between NER and a nonepileptic unrelated strain. Pathologic study included hematoxylin-and-eosin (HE), Kliiver-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 jumpinghnning, 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 k 0.21 seizures in 12 h. Ictal cortical and hippocampal EEGs were characterized by high-voltage spikes followed by diffuse spike-andwave 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% (0146) of the animals in F1,25.5% (1315 1) in F2, and 63.6%(56/88) in backcross progenies exhibited spontaneous tonicclonic 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.

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confidence: 99%

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

Noda¹,

Hashizume

Maihara

et al. 1998

Epilepsia

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“…Various biochemical, histological, and immunohistochemical studies have revealed miscellaneous mo- lecular aspects of cpileptogenesis that are still unknown in humans (21,22). It is difficult, howcver, to deduce a causal relationship between any ol' thcse findings and seizure susceptibility in models.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Mapping of Genes for Epilepsy in NER: A Rat Strain with Tonic‐Clonic Seizures

Maihara¹,

Noda²,

Yamazoe³

et al. 2000

Epilepsia

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Summary:Purpose: NER is a mutant rat strain that exhibits spontancous tonic-clonic convulsions accompanied by epileptic discharges on ictal EEG and serves a s a model for generalized tonic-chic seizures in humans. Our previous experiments have suggested that a major autosomal rccessive gene and several minor genes regulate the inheritance of tonic-chic seizures in NER. The purpose of this study was to confirm the mode of inheritance and to locate the causative genes for epilepsy in NER on the rat genetic map.Methodx We developed F 1 hybrid (F 1) and reciprocal backcross progenics of NER with a seizure-resistant strain, F344, and evaluated their seizure susceptibility under tossingstimulatcd and nonstimulated conditions. Backcross animals were genotyped using simple sequence length polymorphism markers for polymerase chain reactions. Linkage between seizure susceptibility and marker loci was analyzed by x2 statistic tests and by the computer programs MAPMAKER/EXP and MAPM AKER/QTL.Results: Under tossing-stimulating conditions, tonic-clonic scizures were provoked in 90% of NER and 66% of (FI x nimals, but no seizures occurred in the F344, FI, or (F1 x F344) backcross animals. Routine monitoring of nonstimulated animals revealed spontaneous tonic-chic convulsions in 100% of NER and 64.2% of (FI x NER) backcross animals, but no seizures in F344 or F1. Gender effect on seizure susceptibility was negligible in (F1 x NER) backcross in both conditions. Preliminary genome-widc scanning and subscquent precise location of the causative genes revealed seizure susceptibility loci, designated Nerl and Ner2, on rat chromosomes I and 3, respectively.Conclusions: Nerl is a locus that controls the inheritance of spontaneous tonic-clonic seizures in an autosomal recessive mode, whereas Ner2 affects the Occurrence of tossing-induced seizures. Orthologous genes in the vicinity of these loci may be related to epileptogenesis in other species, including humans.

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“…Such external stimuli such as the light, sound and electricity used in the present study have generally been used as a convenient means for inducting convulsive seizures in animal models of epilepsy [8,9,16] At 3 weeks of age DBA/ 2 mice, an audiogenic seizure (AGS) model, have characteristic seizure when stimulated by 1000 cps with 110 dB [18], and the sensitivity to sound stimuli gradually decreases with age [161. GEPR were screened once a week during three successive weeks for susceptibility to sound-induced seizures at intensities of 115-124 dB.…”

Section: Discussionmentioning

confidence: 99%