Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes
Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes
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DOI：
10.1038/82826
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发表时间：
2000-10-01
期刊：
影响因子：
30.8
通讯作者：
Hayashi, JI
中科院分区：
文献类型：
--
作者：
Inoue, K;Nakada, K;Hayashi, JI
携带带有致病性突变的线粒体DNA（mtDNA）的小鼠将提供一个系统，用于研究突变mtDNA如何在组织中传播和分布，从而导致线粒体疾病的表达。然而，没有有效的程序可用于产生这些小鼠。分离不含 mtDNA (rho(0)) 的小鼠细胞，使我们能够将体细胞组织中积累的突变 mtDNA 捕获到重新填充 mtDNA（cybrids）的 rho(0) 细胞中。我们分离了带有缺失线粒体DNA的呼吸缺陷细胞杂种，并将该线粒体DNA引入受精卵中。突变的线粒体DNA通过母系传递，其积累导致多种组织中线粒体功能障碍。此外，大多数小鼠因静脉衰竭而死亡，这表明线粒体DNA突变参与了新疾病的发病机制。
Mice carrying mitochondrial DNA (mtDNA) with pathogenic mutations would provide a system in which to study how mutant mtDNAs are transmitted and distributed in tissues, resulting in expression of mitochondrial diseases. However, no effective procedures are available for the generation of these mice. Isolation of mouse cells without mtDNA (rho(0)) enabled us to trap mutant mtDNA that had accumulated in somatic tissues into rho(0) cells repopulated with mtDNA (cybrids). We isolated respiration-deficient cybrids with mtDNA carrying a deletion and introduced this mtDNA into fertilized eggs. The mutant mtDNA was transmitted maternally, and its accumulation induced mitochondrial dysfunction in various tissues. Moreover, most of these mice died because of venal failure, suggesting the involvement of mtDNA mutations in the pathogeneses of new diseases.