Vlgr1 knockout mice show audiogenic seizure susceptibility
Vlgr1 knockout mice show audiogenic seizure susceptibility
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DOI：
10.1111/j.1471-4159.2004.02875.x
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发表时间：
2005-01
影响因子：
4.7
通讯作者：
H. Yagi;Y. Takamura;T. Yoneda;D. Konno;Y. Akagi;Kazunori Yoshida;Makoto Sato
中科院分区：
文献类型：
--
作者：
H. Yagi;Y. Takamura;T. Yoneda;D. Konno;Y. Akagi;Kazunori Yoshida;Makoto Sato
啮齿类动物对听源性癫痫发作（即由大声噪音引起的反射性癫痫发作）的易感性可通过声启动（使动物在早期发育阶段暴露于强烈的听觉刺激）而诱发。一些小鼠和大鼠品系在没有启动的情况下容易发生听源性癫痫发作，这些已被用作研究癫痫的良好实验模型。在这里，我们鉴定了 Vlgr1d 和 Vlgr1e，它们是 Vlgr1b/MGR1 的新型选择性剪接变体，经过序列分析，它们被证明是来自先前被定性为 Mass1 的基因座的转录本。 Vlgr1（Vlgr1b、Vlgr1d 和 Vlgr1e）mRNA 主要在发育中的小鼠大脑的神经上皮中表达。我们的蛋白质标记实验表明 Vlgr1d 和 Vlgr1e 是分泌分子，而 Vlgr1b 是受体。缺乏 Vlgr1 外显子 2-4 的基因敲除小鼠在没有启动的情况下容易发生听源性癫痫发作，尽管它们的大脑没有明显的组织学异常。这些基因敲除小鼠中 95% 表现出狂奔，这是由大声噪音（11 kHz，105 dB）引发的听源性癫痫发作的惊厥前阶段的典型特征，68% 在出生后 3 周表现出强直性惊厥。我们的单基因小鼠具有独特的遗传背景，可以作为进一步研究癫痫发作的有用工具。
Susceptibility to audiogenic seizures, which 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 these have been used as good experimental models with which to study epilepsies. Here we identified Vlgr1d and Vlgr1e, novel alternatively‐spliced variants of Vlgr1b/MGR1, which, upon sequence analysis, were shown to be transcripts from a locus previously characterized as mass1. Vlgr1 (Vlgr1b, Vlgr1d and Vlgr1e) mRNA is expressed predominantly in the neuroepithelium of the developing mouse brain. Our protein‐tagged experiment suggested that Vlgr1d and Vlgr1e are secretory molecules, while Vlgr1b is a receptor. Knockout mice lacking exons 2–4 of Vlgr1 were susceptible to audiogenic seizures without priming, although there were no apparent histological abnormalities in their brains. Ninety‐five percent of these knockout mice exhibited wild running, a feature typical of the preconvulsive phase of audiogenic seizures triggered by loud noise (11 kHz, 105 dB), and 68% exhibited tonic convulsions at 3 weeks after birth. Our monogenic mice, which have a unique genetic background, serve as a useful tool for further studies on seizures.