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Current progress with mammalian models of mitochondrial DNA disease. | LitMetric

AI Article Synopsis

  • Mitochondrial disorders are a group of inherited diseases that can impact various organ systems and manifest at any age, often due to mutations in either nuclear DNA or mitochondrial DNA (mtDNA).
  • Animal models for studying these diseases have been limited due to the complex characteristics of animal mtDNA, which only recently became amenable to gene editing technologies.
  • This review highlights challenges in developing animal models of mtDNA diseases, discusses current mammalian models, and explores new techniques for targeting DNA-editing enzymes to mitochondria for potential future advancements in the field.

Article Abstract

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.

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Source
http://dx.doi.org/10.1002/jimd.12324DOI Listing

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