Investigation of modifiers for epilepsy by using mouse models

使用小鼠模型研究癫痫修饰因子

基本信息

批准号：
18591174
负责人：
YAMAKAWA Kazuhiro
金额：
$ 2.49万
依托单位：
The Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591174/
关键词：
epilepsy gene sodium channel severe myoclonic epilepsy(SMEI)modiffer febrile seizures plus SCNIA mouse model ナトリウムチャネル SCNIA 遺伝子変異 SMEI コンソミックマウス

项目摘要

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.

严重的肌阵挛性癫痫在婴儿期（SMEI）是由编码电压门控钠通道Alpha-Subunit Type-1，NAV1.1的SCN1A基因突变引起的。 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截短的NAV1.1蛋白的主要阴性作用是SMEI的病理基础。我们还在抑制性神经元而不是兴奋性神经元中特别显示了功能缺陷。此外，我们发现，在野生型小鼠中，Nev1.1位于抑制性神经元子类的轴突和somata中，白细胞蛋白阳性篮细胞。与该机构129背景相比，具有B6遗传背景的SCNLA-KI显示了Severee Severee Spectey Severee表型。通过使用MSM小鼠，我们确定了X-Cromosoms的修饰剂基因座，并通过USIN缩小了该区域，由Toshihiko Shiroishi博士开发的综合小鼠。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

(2007) Na channel gene mutations and epilepsymouse models

(2007)Na通道基因突变与癫痫小鼠模型

DOI：
发表时间：
期刊：
Brain & Development 39(3)
影响因子：
0
作者：
Osaka H;et. al.;Yamakawa K.;Yamakawa K.
通讯作者：
Yamakawa K.

Patients with a sodium channel alpha 1 gene mutation show wide phenotypic variation

DOI：
10.1016/j.eplepsyres.2007.03.018
发表时间：
2007-06
期刊：
Epilepsy Research
影响因子：
2.2
作者：
H. Osaka;I. Ogiwara;E. Mazaki;Nami Okamura;S. Yamashita;M. Iai;M. Yamada;K. Kurosawa;H. Iwamoto;N. Yasui‐Furukori;S. Kaneko;T. Fujiwara;Y. Inoue;K. Yamakawa
通讯作者：
H. Osaka;I. Ogiwara;E. Mazaki;Nami Okamura;S. Yamashita;M. Iai;M. Yamada;K. Kurosawa;H. Iwamoto;N. Yasui‐Furukori;S. Kaneko;T. Fujiwara;Y. Inoue;K. Yamakawa

神経治療学てんかんの分子遺伝学:難治てんかんの治療法開発を目指して

神经治疗癫痫的分子遗传学：旨在开发顽固性癫痫的治疗方法