Transmitochondrial Mice as Models for Mitochondrial DNA-Based Diseases

ミトコンドリアゲノム変異導入マウス Transmitochondrial Mice as Models for Mitochondrial DNA-Based Diseases

- 中田和人 NAKADA Kazuto
- Graduate School of Life and Environmental Sciences, University of Tsukuba
- 林純一 HAYASHI Jun-Ichi
- Graduate School of Life and Environmental Sciences, University of Tsukuba

References (49)
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Author(s)

- 中田和人 NAKADA Kazuto
- Graduate School of Life and Environmental Sciences, University of Tsukuba
- 林純一 HAYASHI Jun-Ichi
- Graduate School of Life and Environmental Sciences, University of Tsukuba

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.<br>

Journal

Experimental Animals

Experimental Animals 60(5), 421-431, 2011-10-01

Japanese Association for Laboratory Animal Science

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ミトコンドリアゲノム変異導入マウス Transmitochondrial Mice as Models for Mitochondrial DNA-Based Diseases

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