Dunn David A, Pinkert Carl A
Department of Biological Sciences, State University of New York, Oswego, NY, USA.
Methods Mol Biol. 2015;1265:255-69. doi: 10.1007/978-1-4939-2288-8_18.
Progress in animal modeling of polymorphisms and mutations in mitochondrial DNA (mtDNA) is not as developed as nuclear transgenesis due to a host of cellular and physiological distinctions. mtDNA mutation modeling is of critical importance as mutations in the mitochondrial genome give rise to a variety of pathological conditions and play a contributing role in many others. Nuclear localization and transcription of mtDNA genes followed by cytoplasmic translation and transport into mitochondria (allotopic expression, AE) provide an opportunity to create in vivo modeling of a targeted mutation in mitochondrial genes and has been suggested as a strategy for gene replacement therapy in patients harboring mitochondrial DNA mutations. Here, we use our AE approach to transgenic mouse modeling of the pathogenic human T8993G mutation in mtATP6 as a case study for designing AE animal models.
由于许多细胞和生理差异，线粒体DNA（mtDNA）多态性和突变的动物模型研究进展不如核转基因技术发达。mtDNA突变建模至关重要，因为线粒体基因组中的突变会引发多种病理状况，并在许多其他疾病中起作用。mtDNA基因的核定位和转录，随后进行细胞质翻译并转运到线粒体中（异位表达，AE），为创建线粒体基因靶向突变的体内模型提供了机会，并已被提议作为患有线粒体DNA突变患者的基因替代治疗策略。在这里，我们使用我们的AE方法对mtATP6中致病性人类T8993G突变进行转基因小鼠建模，作为设计AE动物模型的案例研究。
