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Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease

机译:鼠塞细胞病毒感染加剧了线粒体疾病模型中的复杂IV缺乏症

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The influence of environmental insults on the onset and progression of mitochondrial diseases is unknown. To evaluate the effects of infection on mitochondrial disease we used a mouse model of Leigh Syndrome, where a missense mutation in the Taco1 gene results in the loss of the translation activator of cytochrome c oxidase subunit I (TACO1) protein. The mutation leads to an isolated complex IV deficiency that mimics the disease pathology observed in human patients with TACO1 mutations. We infected Taco1 mutant and wild-type mice with a murine cytomegalovirus and show that a common viral infection exacerbates the complex IV deficiency in a tissue-specific manner. We identified changes in neuromuscular morphology and tissue-specific regulation of the mammalian target of rapamycin pathway in response to viral infection. Taken together, we report for the first time that a common stress condition, such as viral infection, can exacerbate mitochondrial dysfunction in a genetic model of mitochondrial disease.
机译:环境侮辱对线粒体疾病发病和进展的影响是未知的。为了评估感染对线粒体疾病的影响,我们使用了Leigh综合征的小鼠模型,其中TACO1基因中的畸形突变导致细胞色素C氧化酶亚基I(Taco1)蛋白的翻译激活剂的丧失。该突变导致分离的复杂IV缺乏,以模拟人类患者TACO1突变中观察到的疾病病理。我们用鼠塞细胞病毒感染了Taco1突变体和野生型小鼠,表明常见的病毒感染以组织特异性方式加剧了复杂的IV缺乏症。我们鉴定了催乳素途径哺乳动物靶标的神经肌肉形态和组织特异性调节的变化,以应对病毒感染。我们一起服用,我们首次报告了一种常见的压力条件,例如病毒感染,可以加剧线粒体疾病的遗传模型中的线粒体功能障碍。

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