Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration
Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration
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DOI：
10.1073/pnas.0801689105
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发表时间：
2008-04-08
影响因子：
11.1
通讯作者：
McManus, Michael T.
中科院分区：
文献类型：
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作者：
Cuellar, Trinna L.;Davis, Tigwa H.;McManus, Michael T.
microRNA（miRNAs）是一种小的非编码RNA，通过抑制翻译和/或降低mRNA稳定性来抑制靶mRNA。虽然很明显，miRNA和Dicer，一种RNase III酶，是产生成熟miRNA的核心，在神经元的早期发育中发挥作用，但它们在体内有丝分裂后神经元中的作用在很大程度上是未知的。为了确定Dicer在神经元中的作用，我们消融了多巴胺感受神经元中的Dicer。在这些细胞中失去Dicer的小鼠表现出一系列表型，包括共济失调、前肢和后肢紧握、大脑尺寸减小和神经元变小。令人惊讶的是，没有Dicer的多巴胺感受神经元在动物的一生中存活。缺乏深度细胞死亡与其他小鼠模型形成对比，其中Dicer已被消融。这些研究突出了Dicerablation在大脑中的复杂性质，并为研究多巴胺感受神经元功能提供了有用的小鼠模型。
MicroRNAs(miRNAs) are small noncoding RNAs that can act to repress target mRNAs by suppressing translation and/or reducing mRNA stability. Although it is clear that miRNAs and Dicer, an RNase III enzyme that is central to the production of mature miRNAs, have a role in the early development of neurons, their roles in the postmitotic neuron in vivo are largely unknown. To determine the roles of Dicer in neurons, we ablated Dicer in dopaminoceptive neurons. Mice that have lost Dicer in these cells display a range of phenotypes including ataxia, front and hind limb clasping, reduced brain size, and smaller neurons. Surprisingly, dopaminoceptive neurons without Dicer survive over the life of the animal. The lack of profound cell death contrasts with other mouse models in which Dicer has been ablated. These studies highlight the complicated nature of Dicerablation in the brain and provide a useful mouse model for studying dopaminoceptive neuron function.