Gomafu lncRNA knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine.
Gomafu lncRNA knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine.
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Gomafu lncRNA敲除小鼠表现出轻微的多动症，对心理刺激甲基苯丙胺的反应性增强。
DOI：
10.1038/srep27204
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发表时间：
2016-06-02
影响因子：
4.6
通讯作者：
Nakagawa S
中科院分区：
文献类型：
--
作者：
Ip JY;Sone M;Nashiki C;Pan Q;Kitaichi K;Yanaka K;Abe T;Takao K;Miyakawa T;Blencowe BJ;Nakagawa S
长的非编码RNA Gomafu/MIAT/Rncr2被认为在视网膜细胞指定、干细胞分化和控制选择性剪接方面发挥功能。为了进一步研究Gomafu的生理功能，我们建立了完全缺乏Gomafu基因的小鼠基因敲除(KO)模型。KO小鼠没有表现出任何发育缺陷。然而，行为测试显示，KO小鼠是多动的。当精神刺激剂甲基苯丙胺治疗KO小鼠时，这种多动行为得到加强，这与伏隔核多巴胺释放增加有关。RNA测序分析发现了一小部分受Gomafu缺陷影响的基因，其中的一部分已知具有重要的神经生物学功能。这些观察表明，Gomafu通过对基因表达的温和调节和/或靶基因的选择性剪接来改变小鼠的行为。
The long noncoding RNA Gomafu/MIAT/Rncr2 is thought to function in retinal cell specification, stem cell differentiation and the control of alternative splicing. To further investigate physiological functions of Gomafu, we created mouse knockout (KO) model that completely lacks the Gomafu gene. The KO mice did not exhibit any developmental deficits. However, behavioral tests revealed that the KO mice are hyperactive. This hyperactive behavior was enhanced when the KO mice were treated with the psychostimulant methamphetamine, which was associated with an increase in dopamine release in the nucleus accumbens. RNA sequencing analyses identified a small number of genes affected by the deficiency of Gomafu, a subset of which are known to have important neurobiological functions. These observations suggest that Gomafu modifies mouse behavior thorough a mild modulation of gene expression and/or alternative splicing of target genes.