Mitochondrial disorders make up a large class of heritable diseases that cause a broad array of different human pathologies. They can affect many different organ systems, or display very specific tissue presentation, and can lead to illness either in childhood or later in life. While the over 1200 genes encoded in the nuclear DNA play an important role in human mitochondrial disease, it has been known for over 30 years that mutations of the mitochondria's own small, multicopy DNA chromosome (mtDNA) can lead to heritable human diseases. Unfortunately, animal mtDNA has resisted transgenic and directed genome editing technologies until quite recently. As such, animal models to aid in our understanding of these diseases, and to explore preclinical therapeutic research have been quite rare. This review will discuss the unusual properties of animal mitochondria that have hindered the generation of animal models. It will also discuss the existing mammalian models of human mtDNA disease, describe the methods employed in their generation, and will discuss recent advances in the targeting of DNA‐manipulating enzymes to the mitochondria and how these may be employed to generate new models.

中文翻译：

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线粒体 DNA 疾病哺乳动物模型的当前进展

线粒体疾病构成一大类可导致多种不同人类病理的遗传性疾病。它们可以影响许多不同的器官系统，或表现出非常特殊的组织表现，并可能导致儿童期或晚年的疾病。虽然核 DNA 中编码的 1200 多个基因在人类线粒体疾病中发挥重要作用，但 30 多年来，人们已经知道线粒体自身的小型多拷贝 DNA 染色体 (mtDNA) 的突变会导致可遗传的人类疾病。不幸的是，直到最近，动物 mtDNA 还抵制转基因和定向基因组编辑技术。因此，帮助我们了解这些疾病和探索临床前治疗研究的动物模型非常罕见。本综述将讨论阻碍动物模型生成的动物线粒体的不寻常特性。它还将讨论现有的人类 mtDNA 疾病哺乳动物模型，描述它们产生的方法，并将讨论 DNA 操纵酶靶向线粒体的最新进展以及如何利用这些来产生新模型。