Selection of Rodent Species Appropriate for mtDNA Transfer to Generate Transmitochondrial Mito-Mice Expressing Mitochondrial Respiration Defects

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  • Enoki Shunkei
    Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
  • Shimizu Akinori
    Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
  • Hayashi Chisato
    Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
  • Imanishi Hirotake
    Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan Japan Society for the Promotion of Science (JSPS), 8 Ichiban-cho, Chiyoda-ku, Tokyo 102-8472, Japan
  • Hashizume Osamu
    Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
  • Mekada Kazuyuki
    RIKEN BioResource Center, Koyadai 3-1-1, Tsukuba-shi, Ibaraki 305-0074, Japan
  • Suzuki Hitoshi
    Laboratory of Ecology and Genetics, Graduate School of Environmental Earth Science, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-0810, Japan
  • Hashimoto Tetsuo
    Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
  • Nakada Kazuto
    Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
  • Hayashi Jun-Ichi
    Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan

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  • Selection of rodent species appropriate for mtDNA transfer to generate transmitochondrial Mito-mice expressing mitochondrial respiration defect

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Previous reports have shown that transmitochondrial mito-mice with nuclear DNA from Mus musculus and mtDNA from M. spretus do not express respiration defects, whereas those with mtDNA from Rattus norvegicus cannot be generated from ES cybrids with mtDNA from R. norvegicus due to inducing significant respiration defects and resultant losing multipotency. Here, we isolated transmitochondrial cybrids with mtDNA from various rodent species classified between M. spretus and R. norvegicus, and compared the O2 consumption rates. The results showed a strong negative correlation between phylogenetic distance and reduction of O2 consumption rates, which would be due to the coevolution of nuclear and mitochondrial genomes and the resultant incompatibility between the nuclear genome from M. musculus and the mitochondrial genome from the other rodent species. These observations suggested that M. caroli was an appropriate mtDNA donor to generate transmitochondrial mito-mice with nuclear DNA from M. musculus. Then, we generated ES cybrids with M. caroli mtDNA, and found that these ES cybrids expressed respiration defects without losing multipotency and can be used to generate transmitochondrial mito-mice expressing mitochondrial disorders.

Journal

  • Experimental Animals

    Experimental Animals 63 (1), 21-30, 2014

    Japanese Association for Laboratory Animal Science

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