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Updated: May 28, 2026
An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model
Published on: March 9, 2022
Transmitochondrial mice as models for mitochondrial DNA-based diseases
Kazuto Nakada1, Jun-Ichi Hayashi
1Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
Abstract:
Mitochondrial genome (mtDNA) mutations and the resultant mitochondrial respiratory abnormalities are associated with a wide variety of disorders, such as mitochondrial diseases, neurodegenerative diseases, diabetes, and cancer, as well as aging. Generation of model animals carrying mutant mtDNAs is important for understanding the pathophysiological mechanisms of the mtDNA-based diseases. We have succeeded in generating three kinds of mice with pathogenic mutant mtDNAs, named "mito-mice," by the introduction of mitochondria carrying pathogenic mutant mtDNAs into mouse zygotes and mouse embryonic stem (ES) cells. In the case of mito-mice possessing the heteroplasmic state of wild-type mtDNA and pathogenic mtDNA with a large-scale deletion (ΔmtDNA, mito-miceΔ), a high load of ΔmtDNA induced mitochondrial respiration defects in various tissues, resulting in mitochondrial disease phenotypes, such as low body weight, lactic acidosis, ischemia, myopathy, heart block, deafness, male infertility, long-term memory defects, and renal failure. In this review, we summarize generation and clinical phenotypes of three types of mito-mice and we introduce several treatment trials for mitochondrial diseases using mito-miceΔ.
Insights
Researchers created "mito-mice" with mutated mitochondrial DNA (mtDNA) to study mtDNA diseases. These mice exhibit various symptoms, aiding in understanding and treating mitochondrial disorders.
Area of Science:
- Genetics and Molecular Biology
- Cell Biology
- Pathology
Background:
- Mitochondrial genome (mtDNA) mutations are linked to numerous diseases including neurodegeneration, diabetes, cancer, and aging.
- Understanding the pathophysiology of mtDNA-based disorders requires robust animal models.
Purpose of the Study:
- To generate and characterize novel mouse models (mito-mice) carrying pathogenic mtDNA mutations.
- To investigate the phenotypic consequences of specific mtDNA mutations in vivo.
Main Methods:
- Mitochondria with pathogenic mtDNA mutations were introduced into mouse zygotes and embryonic stem (ES) cells.
- Three types of mito-mice were generated, including those with heteroplasmic wild-type and deleted mtDNA (ΔmtDNA).
Main Results:
- Mito-mice with a high load of deleted mtDNA (mito-miceΔ) displayed mitochondrial respiration defects.
- These defects resulted in a spectrum of mitochondrial disease phenotypes, including lactic acidosis, myopathy, heart block, infertility, and renal failure.
- Mito-miceΔ exhibited symptoms such as low body weight, ischemia, deafness, and long-term memory deficits.
Conclusions:
- The generated mito-mice serve as valuable models for studying mtDNA-based diseases.
- These models facilitate the investigation of disease mechanisms and the evaluation of potential therapeutic strategies for mitochondrial disorders.
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