2007 Fiscal Year Final Research Report Summary
Investigation of modifiers for epilepsy by using mouse models
| Project/Area Number |
18591174
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
YAMAKAWA Kazuhiro The Institute of Physical and Chemical Research, Lab. for Neurogenetics, laboratory head (30241235)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGATA Tetsshi RIKEN, Lab. for Neurogenetics, Research Scientist (00338766)
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| Project Period (FY) |
2006 – 2007
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| Keywords | epilepsy / gene / sodium channel / severe myoclonic epilepsy(SMEI) / modiffer / febrile seizures plus / SCNIA / mouse model |
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| Research Abstract |
Severe myoclonic epilepsy in infancy (SMEI) is caused by mutations in the SCN1A gene encoding a voltage-gated sodium channel alpha-subunit type-1, Nav1.1. The mouse with Scnla nonsence mutation (Scnla-KI) that we recently generated and reported (Ogiwara, et. al., J Neurosci 22: 5903-5914, 2007) shows severe epileptic seizures and the homozygote die within 2 weeks.
In Scnla-KI mouse, no Nav1.1 protein is detected indicating that haploinsufficiency, rather than dominant-negative effects of truncated Nav1.1 proteins, is the pathological basis for SMEI. We also showed the functional defects specifically in inhibitory neurons and not in excitatory neurons. Furthermore, we found that in wild-type mouse Nev1.1 is localized at axon and somata of a subclass of inhibitory neurons, parvalbumin-positive basket cells.
The Scnla-KI with B6 genetic background shows severee phenotypes compared to that wit 129 background. By using MSM mice, we identified the modifier gene locus at X-chromosome, and narrowed the region by usin the consomic mouse developed by Dr. Toshihiko Shiroishi.
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[Journal Article] a Circuit Basis for Epileptic Seizures in Mice Carrying an Scnla Gene Mutation.
Author(s)
Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, Takeuchi T, Itohara S, Yanagawa Y, Obata K, Furuichi T, Hensch TK, Yamakawa K.(2007) Nav1.1 Localizes to Axons of Parvalbumin-Positive Inhibitory Interneurons
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Journal Title
Journal of Neuroscience 27(22)
Pages: 5903-5914
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation
Author(s)
Osaka H, Ogiwara I, Mazaki E, Okamura N, Yamashita S, Iai M, Yamada M, Kurosawa, K, Iwamoto H, Yasui-Furukori N, Kaneko S, Fujiwara T, Inoue Y, Yamakawa K.(2007)
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Journal Title
Epilepsy Research 75
Pages: 46-51
Description
「研究成果報告書概要(欧文)」より
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[Book] 脳と発達2007
Author(s)
山川 和弘
Total Pages
3
Publisher
日本小児神経学会
Description
「研究成果報告書概要(和文)」より
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