A comparative analysis of kainate receptor GluK2 and GluK5 knockout mice in a pure genetic background
A comparative analysis of kainate receptor GluK2 and GluK5 knockout mice in a pure genetic background
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纯遗传背景下红藻氨酸受体GluK2和GluK5敲除小鼠的比较分析
DOI：
10.1016/j.bbr.2021.113194
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发表时间：
2021
影响因子：
2.7
通讯作者：
Terunuma Miho
中科院分区：
文献类型：
--
作者：
Iida Izumi;Konno Kohtarou;Natsume Rie;Abe Manabu;Watanabe Masahiko;Sakimura Kenji;Terunuma Miho
海氨酸受体(KARs)是谷氨酸受体家族的成员，调节大脑中的突触功能。尽管已知它们与精神障碍有关，但它们是如何参与这些障碍的仍不清楚。KARs是由GluK1-5亚基组合而成的四聚体通道。其中，GluK2和GluK5亚基是大脑中主要的异构体亚基。为了确定GluK2和GluK5亚基之间的功能异同，我们在C57BL/6N背景下建立了GluK2 KO和GluK5 KO小鼠，并比较了它们的行为表型。我们发现，GluK2 KO和GluK5 KO小鼠在许多测试中表现出相同的表型，例如运动活动减少，运动功能受损，抑郁样行为增强。在运动学习、焦虑样行为或社交能力方面没有观察到变化。此外，我们确定了亚基特定的表型，例如GluK2 KO小鼠对其环境的动机减少，GluK5 KO小鼠的上下文记忆增强。这些结果表明，GluK2和GluK5亚基不仅以一种协调的方式发挥作用，而且在调节行为方面也具有亚基特有的作用。综上所述，我们首次展示了GluK2和GluK5亚基的亚基特异性和共同的行为效应。此外，据我们所知，这是GluK5亚基参与抑郁样行为和背景记忆表达的第一个证据，这有力地表明了它在精神障碍中的作用。
Kainate receptors (KARs) are members of the glutamate receptor family that regulate synaptic function in the brain. Although they are known to be associated with psychiatric disorders, how they are involved in these disorders remains unclear. KARs are tetrameric channels assembled from a combination of GluK1-5 subunits. Among these, GluK2 and GluK5 subunits are the major heteromeric subunits in the brain. To determine the functional similarities and differences between GluK2 and GluK5 subunits, we generated GluK2 KO and GluK5 KO mice on a C57BL/6N background, a well-characterized inbred strain, and compared their behavioral phenotypes. We found that GluK2 KO and GluK5 KO mice exhibited the same phenotypes in many tests, such as reduced locomotor activity, impaired motor function, and enhanced depressive-like behavior. No change was observed in motor learning, anxiety-like behavior, or sociability. Additionally, we identified subunit-specific phenotypes, such as reduced motivation toward their environment in GluK2 KO mice and an enhancement in the contextual memory in GluK5 KO mice. These results revealed that GluK2 and GluK5 subunits not only function in a coordinated manner but also have a subunit-specific role in regulating behavior. To summarize, we demonstrated subunit-specific and common behavioral effects of GluK2 and GluK5 subunits for the first time. Moreover, to the best of our knowledge, this is the first evidence of the involvement of the GluK5 subunit in the expression of depressive-like behavior and contextual memory, which strongly indicates its role in psychiatric disorders.