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Current Progress with Mammalian Models of Mitochondrial DNA Disease

Lookup NU author(s): Dr Jim StewartORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 pre-clinical 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.

Publication metadata

Author(s): Stewart JB

Publication type: Review

Publication status: Published

Journal: Journal of Inherited Metabolic Disease

Year: 2021

Volume: 44

Issue: 2

Pages: 325-342

Print publication date: 01/03/2021

Online publication date: 25/10/2020

Acceptance date: 21/10/2020

ISSN (print): 0141-8955

ISSN (electronic): 1573-2665


DOI: 10.1002/jimd.12324

PubMed id: 33099782