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

Shunkei Enoki; Akinori Shimizu; Chisato Hayashi; Hirotake Imanishi; Osamu Hashizume; Kazuyuki Mekada; Hitoshi Suzuki; Tetsuo Hashimoto; Kazuto Nakada; Jun-Ichi Hayashi

doi:10.1538/expanim.63.21

Originals

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

Shunkei Enoki, Akinori Shimizu, Chisato Hayashi, Hirotake Imanishi, Osamu Hashizume, Kazuyuki Mekada, Hitoshi Suzuki, Tetsuo Hashimoto, Kazuto Nakada, Jun-Ichi Hayashi

Author information

Shunkei Enoki
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
Akinori Shimizu
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
Chisato Hayashi
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
Hirotake Imanishi
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
Osamu Hashizume
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
Kazuyuki Mekada
RIKEN BioResource Center, Koyadai 3-1-1, Tsukuba-shi, Ibaraki 305-0074, Japan
Hitoshi Suzuki
Laboratory of Ecology and Genetics, Graduate School of Environmental Earth Science, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-0810, Japan
Tetsuo Hashimoto
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
Kazuto Nakada
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan
Jun-Ichi Hayashi
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan

Keywords: interspecies mtDNA transfer, multipotency, Mus caroli mtDNA, respiration defects, transmitochondrial ES cybrids

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Supplementary material

2014 Volume 63 Issue 1 Pages 21-30

DOI https://doi.org/10.1538/expanim.63.21

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Abstract

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.

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