Deficiency of Meis1, a transcriptional regulator, in mice and worms: Neurochemical and behavioral characterizations with implications in the restless legs syndrome.
Deficiency of Meis1, a transcriptional regulator, in mice and worms: Neurochemical and behavioral characterizations with implications in the restless legs syndrome.
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DOI：
10.1111/jnc.15177
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发表时间：
2020-12
影响因子：
4.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Lyu S;Xing H;Liu Y;Girdhar P;Zhang K;Yokoi F;Xiao R;Li Y
不宁腿综合征是一种与睡眠相关的感觉运动神经系统疾病，影响多达10%的人口。遗传分析已经确定了髓样嗜亲性病毒整合位点1（MEIS 1），一种转录调节因子，不仅与不宁腿综合征有关，还与自我报告的失眠和睡眠症状有关。本研究旨在确定Meis 1缺陷是否会导致小鼠出现不宁腿综合征样表型，如果是这样，其潜在机制是什么。我们使用了两种遗传模型系统，秀丽隐杆线虫和小鼠。采用卵滞留试验和荧光报告基因技术对C.优雅的。对于小鼠，我们进行了行为测试、血清和脑铁检测、qRT-PCR、蛋白质印迹、免疫组织化学和体外脑切片记录。结果表明，C.在elegans中，dop-3（DRD 2的直系同源物）的功能在敲低unc-62（MEIS 1的直系同源物）后减弱。此外，unc-62敲低导致酪氨酸羟化酶的直向同源物cat-2的转录增强。Meis 1基因敲除小鼠是多动的，并且具有休息期特异性的觉醒概率增加。此外，Meis 1基因敲除小鼠血清铁蛋白增加，纹状体多巴胺能和胆碱能系统改变。具体而言，Meis 1基因敲除小鼠表现出纹状体酪氨酸羟化酶的mRNA水平增加，但蛋白质水平降低。此外，Meis 1基因敲除小鼠纹状体多巴胺周转增加，纹状体胆碱能中间神经元自发放电规律性降低。我们的数据表明，Meis 1基因敲除小鼠具有不宁腿综合征样运动不安和血清铁蛋白水平的变化。这些症状可能与多巴胺能和胆碱能系统功能失调有关。
Restless legs syndrome is a sleep-related sensorimotor neurological disease affecting up to 10% of the population. Genetic analyses have identified Myeloid Ecotropic viral Integration Site 1 (MEIS1), a transcriptional regulator, to be associated with not only the restless legs syndrome but also self-reported symptoms of insomnia and sleep. This study is to determine if Meis1 deficiency in mice can lead to restless legs syndrome-like phenotypes, and if it is the case, what the underlying mechanisms are. We used two genetic model systems, Caenorhabditis elegans and mice. Egg retention assay and fluorescent reporters were used with C. elegans. For mice, we performed behavioral tests, serum and brain iron detection, qRT-PCR, western blot, immunohistochemistry, and in vitro brain-slice recording. Our results showed that with C. elegans, the function of dop-3, an orthologue of DRD2, was diminished after the knockdown of unc-62, an ortholog of MEIS1. Additionally, unc-62 knockdown led to enhanced transcription of the orthologue of tyrosine hydroxylase, cat-2. Meis1 knockout mice were hyperactive and had a rest-phase-specific increased probability of waking. Moreover, Meis1 knockout mice had increased serum ferritin and altered striatal dopaminergic and cholinergic systems. Specifically, Meis1 knockout mice showed an increased mRNA level but decreased protein level of tyrosine hydroxylase in the striatum. Furthermore, Meis1 knockout mice had increased striatal dopamine turnover and decreased spontaneous firing regularity of striatal cholinergic interneurons. Our data suggest that Meis1 knockout mice have restless legs syndrome-like motor restlessness and changes in serum ferritin levels. The symptoms may be related to dysfunctional dopaminergic and cholinergic systems.
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影响因子：
5.3
作者：
Gulyani, Seema;Earley, Christopher J.;Mattson, Mark R.
通讯作者：
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影响因子：
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作者：
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DOI：
10.1006/bbrc.2000.2870
发表时间：
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影响因子：
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作者：
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