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Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes

Nature Genetics 26, 176–181 (2000) | Download Citation

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Abstract

Mice carrying mitochondrial DNA (mtDNA) with pathogenic mutations would provide a system in which to study how mutant mtDNAs are transmitted and distributed in tissues, resulting in expression of mitochondrial diseases. However, no effective procedures are available for the generation of these mice. Isolation of mouse cells without mtDNA (ρ0) enabled us to trap mutant mtDNA that had accumulated in somatic tissues into ρ0 cells repopulated with mtDNA (cybrids). We isolated respiration-deficient cybrids with mtDNA carrying a deletion and introduced this mtDNA into fertilized eggs. The mutant mtDNA was transmitted maternally, and its accumulation induced mitochondrial dysfunction in various tissues. Moreover, most of these mice died because of renal failure, suggesting the involvement of mtDNA mutations in the pathogeneses of new diseases.

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Author information

    • Kimiko Inoue
    •  & Kazuto Nakada

    These authors contributed equally to this work.

Affiliations

  1. Institute of Biological Sciences, University of Tsukuba, Ibaraki, Japan.

    • Kimiko Inoue
    • , Kazuto Nakada
    • , Kotoyo Isobe
    •  & Jun-Ichi Hayashi

  2. Center for Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki, Japan.

    • Jun-Ichi Hayashi

  3. Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo, Japan.

    • Kimiko Inoue
    •  & Atsuo Ogura

  4. Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.

    • Yu-ichi Goto

  5. Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.

    • Kazuto Nakada
    •  & Ikuya Nonaka

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Correspondence to Jun-Ichi Hayashi.

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DOI

https://doi.org/10.1038/82826