G7731A mutation in mouse mitochondrial tRNALys regulates late-onset disorders in transmitochondrial mice.
G7731A mutation in mouse mitochondrial tRNALys regulates late-onset disorders in transmitochondrial mice.
复制标题
小鼠线粒体 tRNALys 中的 G7731A 突变可调节跨软骨小鼠的迟发性疾病。
DOI：
10.1016/j.bbrc.2015.02.070
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发表时间：
2015
影响因子：
3.1
通讯作者：
Hayashi J-I
中科院分区：
文献类型：
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作者：
Shimizu A;Mito T;Hashizume O;Yonekawa H;Ishikawa K;Nakada K;Hayashi J-I
我们先前产生了线粒体-小鼠-tRNALys 7731作为线粒体疾病的一级预防的模型。这些小鼠在tRNALysgene中携带G7731 A mtDNA突变，但在4个月时仅表现出肌肉无力和短体长。在这里，我们研究了他们的新陈代谢和组织学特征的老化的影响。与年轻的mito-小鼠-tRNALys 7731不同，老年的mito-小鼠-tRNALys 7731出现了肌肉萎缩、肾衰竭和各种代谢异常，如乳酸酸中毒和贫血，这是线粒体疾病患者的特征。这些观察结果提供了令人信服的证据，高G7731 A mtDNA水平诱导的呼吸缺陷导致这些迟发性疾病，是相关的线粒体疾病。
We previously generated mito-mice-tRNALys7731as a model for primary prevention of mitochondrial diseases. These mice harbour a G7731A mtDNA mutation in thetRNALysgene, but express only muscle weakness and short body length by four months. Here, we examined the effects of their aging on metabolic and histologic features. Unlike young mito-mice-tRNALys7731, aged mito-mice-tRNALys7731developed muscle atrophy, renal failures, and various metabolic abnormalities, such as lactic acidosis and anemia, characteristic of patients with mitochondrial diseases. These observations provide convincing evidence that the respiration defects induced by high G7731A mtDNA levels cause these late-onset disorders that are relevant to mitochondrial diseases.