Myg1-deficient mice display alterations in stress-induced responses and reduction of sex-dependent behavioural differences
Myg1-deficient mice display alterations in stress-induced responses and reduction of sex-dependent behavioural differences
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DOI：
10.1016/j.bbr.2009.10.005
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发表时间：
2010-02-11
影响因子：
2.7
通讯作者：
Vasar, Eero
中科院分区：
文献类型：
--
作者：
Philips, Mari-Anne;Abramov, Urho;Vasar, Eero
Myg1（黑色素细胞增殖基因1）是一个高度保守且普遍表达的基因，其编码的蛋白具有线粒体和核定位。在目前的研究中，我们证明了Myg1在小鼠大脑出生后发育过程中的表达逐渐下降，这表明Myg1与发育过程有关。为了研究Myg1功能丧失的影响，我们通过替换该基因的整个编码序列来创建Myg1缺陷（-/-）小鼠。最初的表型分析涵盖了行为、认知、神经、生理和应激相关的多种反应，揭示了纯合子Myg1（-/-）小鼠是至关重要的、可生育的，并且没有明显的异常。在不同的测试中，Myg1（-/-）小鼠表现出不一致的焦虑样行为改变模式。加迷宫和社会互动测试显示，雄性Myg1（-/-）小鼠的焦虑程度明显低于野生型小鼠；雌性（-/-）小鼠在运动活动领域表现出增加的焦虑。抑制应激显著降低了雌性野生型小鼠前额叶皮层Myg1基因的表达，抑制雌性（-/-）小鼠皮质酮反应减弱，提示Myg1参与应激诱导反应。本研究的主要发现是Myg1的失活减少了雄性和雌性动物之间的几种行为差异，这些差异在野生型小鼠中很明显，这表明Myg1有助于小鼠性别依赖性行为差异的表达。综上所述，我们提供了Myg1参与焦虑和压力相关反应的证据，并表明Myg1有助于性别依赖性行为差异的表达。(C) 2009 Elsevier B.V.版权所有
Myg1 (Melanocyte proliferating gene 1) is a highly conserved and ubiquitously expressed gene, which encodes a protein with mitochondrial and nuclear localization. In the current study we demonstrate a gradual decline of Myg1 expression during the postnatal development of the mouse brain that suggests relevance for Myg1 in developmental processes. To study the effects of Myg1 loss-of-function, we created Myg1-deficient (-/-) mice by displacing the entire coding sequence of the gene. Initial phenotyping, covering a multitude of behavioural, cognitive, neurological, physiological and stress-related responses, revealed that homozygous Myg1 (-/-) mice are vital, fertile and display no gross abnormalities. Myg1 (-/-) mice showed an inconsistent pattern of altered anxiety-like behaviour in different tests. The plus-maze and social interaction tests revealed that male Myg1 (-/-) mice were significantly less anxious than their wild-type littermates; female (-/-) mice showed increased anxiety in the locomotor activity arena. Restraint-stress significantly reduced the expression of the Myg1 gene in the prefrontal cortex of female wild-type mice and restrained female (-/-) mice showed a blunted corticosterone response, suggesting involvement of Myg1 in stress-induced responses. The main finding of the present study was that Myg1 invalidation decreases several behavioural differences between male and female animals that were obvious in wild-type mice, indicating that Myg1 contributes to the expression of sex-dependent behavioural differences in mice. Taken together, we provide evidence for the involvement of Myg1 in anxiety- and stress-related responses and suggest that Myg1 contributes to the expression of sex-dependent behavioural differences. (C) 2009 Elsevier B.V. All rights reserved.