| RRC ID |
2808
|
| 著者 |
Tokuda S, Kuramoto T, Tanaka K, Kaneko S, Takeuchi IK, Sasa M, Serikawa T.
|
| タイトル |
The ataxic groggy rat has a missense mutation in the P/Q-type voltage-gated Ca2+ channel alpha1A subunit gene and exhibits absence seizures.
|
| ジャーナル |
Brain Res
|
| Abstract |
The groggy rat (strain name; GRY) exhibits ataxia, an unstable gait, and paroxysmal severe extension of the entire body. Adults show a reduction in size of the cerebellum and presynaptic and axon terminal abnormalities of Purkinje cells. These neurological abnormalities are inherited in an autosomal recessive manner, and the causative mutation has been named groggy (gry). In this study, we mapped gry on rat chromosome 19 and found a nonconservative missense (M251K) mutation in the alpha(1A) subunit of the P/Q-type voltage-gated Ca(2+) channel gene (Cacna1a) within the gry-critical region. This mutation was located at a highly conserved site close to the ion-selective pore and led to the shortening of the inactivation phase of the Ca(2+) channel current without a change of peak current density or current-voltage relationship in whole cell patch recordings of the recombinant Ca(2+) channel expressed in HEK cells. It has been well established that mice with a mutation at Cacna1a such as tottering and leaner show absence seizures. The Cacna1a-mutant GRY rat also exhibited absence-like seizures from 6 to 8 weeks of age, which were characterized by bilateral and synchronous 7-8 Hz spike-and-wave discharges concomitant with sudden immobility and staring, on cortical and hippocampal EEGs. The pharmacological profile of the seizures was similar to that of human absence epilepsy: the seizures were inhibited by ethosuximide and valproic acid but not phenytoin. Thus, the GRY rat with P/Q-type Ca(2+) channel disorders is a useful model for studying absence epilepsy and Cacna1a-related diseases.
|
| 巻・号 |
1133(1)
|
| ページ |
168-77
|
| 公開日 |
2007-2-16
|
| DOI |
10.1016/j.brainres.2006.10.086
|
| PII |
S0006-8993(06)03169-6
|
| PMID |
17196942
|
| MeSH |
Animals
Ataxia / genetics*
Ataxia / metabolism
Ataxia / physiopathology
Brain / metabolism*
Brain / physiopathology
Calcium Channels / chemistry
Calcium Channels / genetics*
Calcium Channels, P-Type / chemistry
Calcium Channels, P-Type / genetics*
Cell Line
Cell Membrane / chemistry
Cell Membrane / genetics
Cerebral Cortex / metabolism
Cerebral Cortex / physiopathology
Electroencephalography
Epilepsy, Absence / genetics*
Epilepsy, Absence / metabolism
Epilepsy, Absence / physiopathology
Female
Hippocampus / metabolism
Hippocampus / physiopathology
Humans
Male
Membrane Potentials / genetics
Mutation, Missense / genetics*
Patch-Clamp Techniques
Rats
Rats, Mutant Strains
|
| IF |
2.733
|
| 引用数 |
28
|
|
WOS 分野
|
NEUROSCIENCES
|
| リソース情報 |
| ラット |
GRY/Idr(strainID=498)
BN/SsNSlc(strainID=371) |
