Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
Exp Anim. 2014;63(1):21-30. doi: 10.1538/expanim.63.21.
Previous reports have shown that transmitochondrial mito-mice with nuclear DNA from Mus musculus and mtDNA from M. spretus do not express respiration defects, whereas those with mtDNA from Rattus norvegicus cannot be generated from ES cybrids with mtDNA from R. norvegicus due to inducing significant respiration defects and resultant losing multipotency. Here, we isolated transmitochondrial cybrids with mtDNA from various rodent species classified between M. spretus and R. norvegicus, and compared the O2 consumption rates. The results showed a strong negative correlation between phylogenetic distance and reduction of O2 consumption rates, which would be due to the coevolution of nuclear and mitochondrial genomes and the resultant incompatibility between the nuclear genome from M. musculus and the mitochondrial genome from the other rodent species. These observations suggested that M. caroli was an appropriate mtDNA donor to generate transmitochondrial mito-mice with nuclear DNA from M. musculus. Then, we generated ES cybrids with M. caroli mtDNA, and found that these ES cybrids expressed respiration defects without losing multipotency and can be used to generate transmitochondrial mito-mice expressing mitochondrial disorders.
先前的报告表明，携带有来自 Mus musculus 的核 DNA 和来自 M. spretus 的 mtDNA 的线粒体转移小鼠不会表现出呼吸缺陷，而那些携带有来自 Rattus norvegicus 的 mtDNA 的线粒体转移小鼠则由于诱导出显著的呼吸缺陷和随之而来的多能性丧失，无法从带有来自 R. norvegicus 的 mtDNA 的 ES 细胞杂交体中生成。在这里，我们分离了携带有来自 M. spretus 和 R. norvegicus 之间的各种啮齿动物物种的 mtDNA 的线粒体转移杂交体，并比较了它们的 O2 消耗率。结果表明，亲缘关系和 O2 消耗率的降低之间存在强烈的负相关，这可能是由于核基因组和线粒体基因组的共同进化以及来自 M. musculus 的核基因组与其他啮齿动物物种的线粒体基因组之间的不兼容性所致。这些观察结果表明，M. caroli 是一种合适的 mtDNA 供体，可以生成携带有来自 M. musculus 的核 DNA 的线粒体转移小鼠。然后，我们生成了带有 M. caroli mtDNA 的 ES 细胞杂交体，并发现这些 ES 细胞杂交体表现出呼吸缺陷而没有丧失多能性，并且可以用于生成表达线粒体疾病的线粒体转移小鼠。
