Japanese
English
- 有料閲覧
- Abstract 文献概要
- 1ページ目 Look Inside
筆者らは胎生期の中枢神経の神経上皮に特異的に発現する新規分子を同定,ノックアウトマウスを作製し,機能解析を進めてきた。同定した分子は後にVlgr1(very large G-protein coupled receptor 1)のスプライシングバリアントと判明したが,筆者らのノックアウトマウスは同時に機能が明らかとなっていないVlgr1をも欠損していた。筆者らは,このVlgr1遺伝子欠損マウスが聴原性てんかんに高い感受性があることを明らかにした。齧歯類に認められる聴原性てんかんは,全身性のけいれんを起こすてんかんのモデルのひとつとも考えられ,研究の対象となってきた。今回,聴原性てんかんに関する諸家の報告を俯瞰するとともに,同てんかんに高感受性を認めるDBA/2系統と筆者らのマウスとを比較し,その原因解明へ向けた現在までのデータを紹介した。聴原性てんかんの根本原因は明らかとなっていないが,けいれん発現までには,脳内の多くの回路が関わり,さらにその一部はモデルマウスを越え共通であることが判明した。
Susceptibility to audiogenic seizures, that are reflex seizures provoked by loud noise, can be induced in rodents by acoustic priming(exposing animals to strong auditory stimuli at an early developmental stage). Some strains of mice and rats are susceptible to audiogenic seizures without priming, and they have been used as good experimental models with which to study epilepsies. By searching for ventricular zone(neuroepithelium)-specifically expressing genes, we identified two novel molecules. Later, they turned out to be Vlgr1d and Vlgr1e, novel alternatively spliced variants of Vlgr1b, which upon sequence analysis were shown to be transcripts from a locus, characterized as mass1. Vlgr1(Vlgr1b, Vlgr1d and Vlgr1e)mRNA is expressed predominantly in the neuroepithelium of the developing mouse brain. Up to now, their function remains unknown, although Vlgr1(very large G-protein coupled receptor)is predicted to be a G-protein coupled receptor and Vlgr1d and Vlgr1e are secretory molecules, based on their cDNA sequences. We then studied the function of Vlgr1 using gene targeting method. Our knockout mouse(Vlgr1 mutated mouse)in which the expression of Vlgr1 was disrupted showed high susceptibility to audiogenic seizures without priming. In this article, we summarize the previously reported studies on audiogenic seizures, then compared our data on our Vlgr1 mutated mice, especially with the reported phenotype of DBA/2 mice that is highly susceptible to audiogenic seizures.
Copyright © 2005, Igaku-Shoin Ltd. All rights reserved.