Attempts to understand the mechanisms of mitochondrial diseases: the reverse genetics of mouse models for mitochondrial disease

Ishikawa, Kaori; Nakada, Kazuto

doi:10.1016/j.bbagen.2020.129835

Cited by 9Mitochondrial Function and PathologyMetabolism and Genetic DisordersAutophagy in Disease and Therapy

Attempts to understand the mechanisms of mitochondrial diseases: the reverse genetics of mouse models for mitochondrial disease

Ishikawa, Kaori, Nakada, Kazuto·2021·Biochimica et Biophysica Acta (BBA) - General Subjects

DOI 10.1016/j.bbagen.2020.129835

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Abstract

Background Mitochondrial disease is a general term for a disease caused by a decline in mitochondrial function. The pathology of this disease is extremely diverse and complex, and the mechanism of its pathogenesis is still unknown. Using mouse models that develop the disease via the same processes as in humans is the easiest path to understanding the underlying mechanism. However, creating a mouse model is extremely difficult due to the lack of technologies that enable editing of mitochondrial DNA (mtDNA).Scope of review This paper outlines the complex pathogenesis of mitochondrial disease, and the difficulties in producing relevant mouse models. Then, the paper provides a detailed discussion on several mice created with mutations in mtDNA. The paper also introduces the pathology of mouse models with mutations including knockouts of nuclear genes that directly affect mitochondrial function.Major conclusions Several mice with mtDNA mutations and those with nuclear DNA mutations have been established. Although these models help elucidate the pathological mechanism of mitochondrial disease, they lack sufficient diversity to enable a complete understanding. Considering the variety of factors that affect the cause and mechanism of mitochondrial disease, it is necessary to account for this background diversity in mouse models as well.General significance Mouse models are indispensable for understanding the pathological mechanism of mitochondrial disease, as well as for searching new treatments. There is a need for the creation and examination of mouse models with more diverse mutations and altered nuclear backgrounds and breeding environments.

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Mitochondrial diseases are caused by genetic mutations in mitochondrial or nuclear DNA that affect the function of the mitochondrial respiratory chain, leading to defective oxidative phosphorylation.
“Mitochondrial diseases are caused by genetic mutations in mitochondrial or nuclear DNA that affect the function of the mitochondrial respiratory chain, thereby leading to defective oxidative phosphorylation (Ishikawa and Nakada, 2021; Parikh et al., 2015; Thorburn, 2004).”
From Impaired aerobic capacity and premature fatigue preceding muscle weakness in the skeletal muscle <i>Tfam-</i>knockout mouse model (2021) · cites this paper as Ishikawa and Nakada, 2021

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Disease models of Leigh syndrome: From yeast to organoids
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Self-citation
Animal Model Selection and Deep Phenotyping in Mitochondrial Genetic Diseases: Connecting Human Variants, Multisystem Pathology, and Preclinical Evidence
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Authors: Ishikawa, K., & Nakada, K.
Affiliations: University of Tsukuba (JP)
Corresponding author: Nakada, Kazuto
ORCID: Ishikawa, Kaori
Nakada, Kazuto
Venue: Biochimica et Biophysica Acta (BBA) - General Subjects
Publisher: Elsevier BV
Published: 2021-03
Volume: 1865
Issue: 3
Pages: 129835
ISSN: 0304-4165 (ISSN-L)
DOI: 10.1016/j.bbagen.2020.129835
OpenAlex: W3115762724
Cited by: 9
References: 110
Citations by year: 2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1
FWCI: 0.24
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
PubMed (publishedVersion)
Funders: Takeda Science Foundation
Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords: mitochondrial disease, mouse model, mitochondrial DNA mutations, reverse genetics, mitochondrial DNA editing, breeding habitat
MeSH terms: Maternal Inheritance, Animals, Chromosome Mapping, Disease Models, Animal, DNA, Mitochondrial, Humans, Mitochondria, Mutation, Organ Specificity, Severity of Illness Index, Species Specificity, Cloning, Organism, Mitochondrial Diseases, Mice, Genome, Mitochondrial, Reverse Genetics

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Attempts to understand the mechanisms of mitochondrial diseases: the reverse genetics of mouse models for mitochondrial disease

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