RNF8 deficiency results in neurodegeneration in mice.
RNF8 deficiency results in neurodegeneration in mice.
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RNF8 缺乏导致小鼠神经退行性变
DOI：
10.1016/j.neurobiolaging.2015.07.010
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发表时间：
2015-10
影响因子：
4.2
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Ouyang S;Song Y;Tian Y;Chen Y;Yu X;Wang D
神经元的进行性丧失会导致神经退行性疾病。由于DNA断裂的积累导致神经细胞的凋亡，各种DNA损伤修复相关蛋白的缺乏导致了神经退行性变。泛素连接酶RNF8通过组蛋白泛素化在DNA双链断裂修复中发挥重要作用。然而，RNF8在终末分化神经元中的功能仍不清楚。本研究旨在确定RNF8是否参与神经元的DNA损伤反应并促进神经变性。在这里，我们提出的证据表明，RNF8缺乏导致DNA损伤积累和神经元凋亡。RNF8−/−小鼠表现为神经元变性和反应性星形细胞增多。来自rnf8−/−小鼠的神经元似乎更容易受到X射线诱导的dna损伤。这些变化与RNF8缺陷小鼠的行为表现一致，包括在开场测试和跳台回避任务中的表现受损。总体而言，这些发现表明，RNF8是神经元DNA损伤修复所必需的。RNF8缺乏足以导致神经元病理和认知功能下降，RNF8缺失会导致神经元变性。
The progressive loss of neurons causes neurodegenerative diseases. Because the accumulation of DNA breaks results in neuronal apoptosis, the lack of a variety of DNA damage repair-related proteins contributes to neurodegeneration. The ubiquitin ligase RNF8 plays an important role in DNA double-strand break repair via histone ubiquitination. However, the function of RNF8 in terminally differentiated neurons remains unknown. This study aimed to determine whether RNF8 is involved in the DNA damage response in neurons and contributes to neurodegeneration. Here, we present evidence suggesting that RNF8 deficiency results in DNA damage accumulation and neuronal apoptosis. RNF8−/−mice exhibit neuronal degeneration and reactive astrocytosis. Neurons from RNF8−/− mice appear to be more susceptible to X-ray-induced DNA damage. These changes were consistent with the behavioral performances of the RNF8-deficient mice, which included impaired performances in the open-field test and step-down avoidance task. Overall, these findings show that RNF8 is required for DNA damage repair in neurons. RNF8 deficiency is sufficient to cause neuronal pathology and cognitive decline, and the loss of RNF8 results in neuron degeneration.