Deletion-mutant mtDNA increases in somatic tissues but decreases in female germ cells with age
Deletion-mutant mtDNA increases in somatic tissues but decreases in female germ cells with age
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DOI：
10.1534/genetics.107.081026
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发表时间：
2007-12-01
期刊：
影响因子：
3.3
通讯作者：
Hayashi, Jun-Ichi
中科院分区：
文献类型：
--
作者：
Sato, Akitsugu;Nakada, Kazuto;Hayashi, Jun-Ichi
变种人的比例。和野生型mtDNA在确定线粒体疾病的严重程度方面至关重要。人们普遍认为，缺失突变体mtDNA具有复制优势，并随时间积累。在这里，我们检测了线粒体疾病模型小鼠（mitto -小鼠）中4696 bp缺失的突变mtDNA （Delta mtDNA）和野生型mtDNA的组织比例。比较不同年龄各组织中Delta mtDNA的比例表明，Delta mtDNA的积累速度在各组织中存在差异。心脏、骨骼肌、肾脏、肝脏、睾丸和卵巢的Delta mtDNA比例随着年龄的增长而增加，但胰腺、脾脏、大脑和血液的比例仅略有增加或没有增加。然而，与体细胞组织相反，雌性有丝分裂小鼠的生殖细胞及其后代的Delta mtDNA随着母亲年龄的增长而明显减少。这种减少是如此剧烈，以至于一些后代显示出Delta mtDNA完全消失，即使他们的哥哥和姐姐有很高比例的Delta mtDNA。女性生殖细胞有一种机制，可以防止有缺陷的mtDNA遗传给下一代，因为生殖细胞被保存了很长一段时间，直到它们排卵。
The proportions Of mutant. and wild-type mtDNA are crucial in determining the severity of mitochondrial diseases. It has been generally considered that deletion-mutant mtDNA has replication advantages and accumulates with time. Here, we examine the tissue-by-tissue Proportions Of mutant mtDNA with a 4696-bp deletion (Delta mtDNA) and wild-type mtDNA in mitochondrial disease model mice (mito-mice). Comparison Of the proportions of Delta mtDNA in each tissue at various ages showed that the rate of accumulation of Delta mtDNA differed among tissues. The heart, skeletal muscles, kidney, liver, testis, and ovary, showed increases in the proportion of Delta mtDNA with age, but the pancreas, spleen, brain, and blood showed only a slight or no increase in proportion. In contrast to the somatic tissues, however, the germ cells of female mito-mice and resultant offspring showed a strong decrease in Delta mtDNA with maternal age. The decrease was so acute that some offspring showed complete disappearance of Delta mtDNA, even though their elder brothers and sisters had high proportions of Delta mtDNA. Female germ cells have a machinery that prevents the inheritence of defective mtDNA to the following generation since germ cells are kept for a long time until they are ovulated.