Research development and the prospect of animal models of mitochondrial DNA-related mitochondrial diseases.

ABSTRACT

Mitochondrial diseases (MDs) are genetic and clinical heterogeneous diseases caused by mitochondrial oxidative phosphorylation defects. It is not only one of the most common genetic diseases, but also the only genetic disease involving two different genomes in humans. As a result of the complicated genetic condition, the pathogenesis of MDs is not entirely elucidated at present, and there is a lack of effective treatment in the clinic. Establishing the ideal animal models is the critical preclinical platform to explore the pathogenesis of MDs and to verify new therapeutic strategies. However, the development of animal modeling of mitochondrial DNA (mtDNA)-related MDs is time-consuming due to the limitations of physiological structure and technology. A small number of animal models of mtDNA mutations have been constructed using cell hybridization and other methods. However, the diversity of mtDNA mutation sites and clinical phenotypes make establishing relevant animal models tricky. The development of gene editing technology has become a new hope for establishing animal models of mtDNA-related mitochondrial diseases.