Deletion of Long Isoform of Eukaryotic Elongation Factor 1Bδ Leads to Audiogenic Seizures and Aversive Stimulus-Induced Long-Lasting Activity Suppression in Mice.
Deletion of Long Isoform of Eukaryotic Elongation Factor 1Bδ Leads to Audiogenic Seizures and Aversive Stimulus-Induced Long-Lasting Activity Suppression in Mice.
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DOI：
10.3389/fnmol.2018.00358
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发表时间：
2018
影响因子：
4.8
通讯作者：
Matsushita M
中科院分区：
文献类型：
--
作者：
Kaitsuka T;Kiyonari H;Shiraishi A;Tomizawa K;Matsushita M
选择性剪接使基因能够产生不同的蛋白质产物。Eef 1d基因产生两种亚型：编码翻译延伸因子1Bδ（eEF 1B δ1）的短亚型和编码热休克应答转录因子eEF 1B δL的长亚型。此前，我们发现eEF 1B δL是一种剪接变体，特异于大脑和睾丸，编码的蛋白质被认为在中枢神经系统中具有功能。在这项研究中，我们产生敲除（KO）小鼠的C57 BL/6 J背景，选择性缺乏一个特定的外显子Eef 1d的长亚型。这些KO小鼠在脑中缺乏eEF 1B δL，但不缺乏eEF 1B δ1。尽管KO小鼠在行为测试中表现出正常的焦虑相关行为和学习行为，但有些小鼠对响亮的声音（90 dBA）表现出严重的癫痫发作，这是一种听源性癫痫发作（AGS）反应。此外，在KO小鼠进行恐惧条件反射测试后，它们在其家笼中以及在旷场和高架十字迷宫测试中显示出显著降低的运动活动。在恐惧条件反射测试后，在KO小鼠中观察到脑重量显著降低、海马和中脑萎缩以及皮质层厚度减少。我们还发现，在这些小鼠中，随着内质网应激标志物的诱导，eEF 1B δ1水平和蛋白质合成的升高出现代偿性增加。我们的研究结果表明，eEF 1B δL在正常脑功能中具有重要作用，特别是当暴露于外部刺激时。
Alternative splicing enables a gene to give rise to diverse protein products. The Eef1d gene produces two isoforms: a short isoform that encodes translation elongation factor 1Bδ (eEF1Bδ1), and a long isoform that encodes the heat shock-responsive transcription factor eEF1BδL. Previously, we found that eEF1BδL was a splice variant that was specific to the brain and testis, and the protein encoded is thought to have a function in the central nervous system. In this study, we generated knockout (KO) mice of C57BL/6J background that selectively lacked a specific exon in Eef1d for the long isoform. These KO mice lacked eEF1BδL, but not eEF1Bδ1, in the brain. Although the KO mice showed normal anxiety-related and learning behavior in behavioral tests, some showed severe seizures in response to loud sounds (90 dBA), an audiogenic seizures (AGS) response. Furthermore, after the KO mice had been subjected to the fear conditioning test, they showed remarkably decreased locomotor activity in their home cage and in the open-field and elevated plus-maze tests. After the fear conditioning test, a significant decrease in brain weight, atrophy of the hippocampus and midbrain, and reduced cortical layer thickness were observed in the KO mice. We also found a compensatory increase in the eEF1Bδ1 level and elevated protein synthesis with the induction of endoplasmic reticulum stress markers in these mice. Our results suggest that eEF1BδL has an important role in normal brain function especially when exposed to external stimuli.
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影响因子：
3.7
作者：
Nosten-Bertrand M;Kappeler C;Dinocourt C;Denis C;Germain J;Phan Dinh Tuy F;Verstraeten S;Alvarez C;Métin C;Chelly J;Giros B;Miles R;Depaulis A;Francis F
通讯作者：
Francis F
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.3791/1088
发表时间：
2008-12-22
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Komada, Munekazu;Takao, Keizo;Miyakawa, Tsuyoshi
通讯作者：
Miyakawa, Tsuyoshi
影响因子：
7.7
作者：
Kaitsuka, Taku;Tomizawa, Kazuhito;Matsushita, Masayuki
通讯作者：
Matsushita, Masayuki
影响因子：
9.8
作者：
Ortiz-Abalia, Jon;Sahun, Ignasi;Fillat, Cristina
通讯作者：
Fillat, Cristina