Metabotropic glutamate receptor subtype-1 is essential for motor coordination in the adult cerebellum
Metabotropic glutamate receptor subtype-1 is essential for motor coordination in the adult cerebellum
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DOI：
10.1016/j.neures.2006.12.014
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发表时间：
2007-04-01
影响因子：
2.9
通讯作者：
Aiba, Atsu
中科院分区：
文献类型：
--
作者：
Nakao, Harumi;Nakao, Kazuki;Aiba, Atsu
我们之前证明，代谢性谷氨酸受体亚型1敲除[mGluR1(-/-)]小鼠表现出步态失调、长期抑郁缺陷和突触消除受损，这些表型通过引入带有浦肯野细胞特异性启动子的mGluR1转基因（mGluR1-拯救小鼠）得以恢复。然而，mGluR1在成人大脑中的作用尚不清楚，主要是由于缺乏常规和可重复的方法来阻止mGIuR1在某一发育阶段的表达。在此，我们利用四环素控制的基因表达系统建立了mGluR1条件敲除（cKO）小鼠的多功能小鼠系，以了解mGluR1在成人大脑中的作用。mGluR1 cKO小鼠仅在浦肯野细胞中表达mGluR1，运动协调正常。在成年mGluR1 cKO小鼠中，mGluR1的表达被阻断导致运动协调功能受损，这表明mGluR1不仅在出生后发育过程中对小鼠的小脑功能至关重要，而且在成年期也是如此。(c) 2007爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
We previously demonstrated that metabotropic glutamate receptor-subtype I knockout [mGluR1 (-/-)] mice showed ataxic gait, deficient long-term depression and impaired synapse elimination and these phenotypes were rescued by introduction of an mGluR1 transgene with Purkinje cell-specific promoter (mGluR1-rescue mice). However, roles of mGluR1 in the adult brain remain elusive, mainly due to lack of conventional and reproducible method to block mGIuR1 expression at a certain developmental stage. Here, we established a versatile mouse line, mGluR1 conditional knockout (cKO) mice using the tetracycline-controlled gene expression system to understand the roles of mGluR1 in the adult brain. The mGluR1 cKO mice express mGluR1 only in Purkinje cells and show normal motor coordination. Blockade of expression of mGluR1 in the adult mGluR1 cKO mice led to impaired motor coordination, suggesting that mGluR1 is essential for cerebellar function in mice not only during postnatal development but also in adulthood. (c) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.