Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic G13997A mtDNA from highly metastatic lung carcinoma cells

Yokota, Mutsumi; Shitara, Hiroshi; Hashizume, Osamu; Ishikawa, Kaori; Nakada, Kazuto; Ishii, Rie; Taya, Choji; Takenaga, Keizo; Yonekawa, Hiromichi; Hayashi, Jun-Ichi

doi:10.1016/j.febslet.2010.07.048

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Volume 584, Issue 18 , Pages 3943-3948, 24 September 2010

Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic G13997A mtDNA from highly metastatic lung carcinoma cells

Edited by Angel Nebreda

Mutsumi Yokota
- Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan
- Japan Society for the Promotion of Science (JSPS), 8 Ichiban-cho, Chiyoda-ku, Tokyo 102-8472, Japan
- Both authors contributed equally to this study.
Hiroshi Shitara
- Laboratory for Transgenic Technology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan
- Both authors contributed equally to this study.
Osamu Hashizume
- Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan
Kaori Ishikawa
- Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan
Kazuto Nakada
- Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan
Rie Ishii
- Laboratory for Transgenic Technology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan
Choji Taya
- Laboratory for Transgenic Technology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan
Keizo Takenaga
- Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan
Hiromichi Yonekawa
- Laboratory for Transgenic Technology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan
Jun-Ichi Hayashi
- Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan
- Corresponding author. Fax: +81 298536650.

Received 24 June 2010; received in revised form 22 July 2010; accepted 23 July 2010. published online 30 July 2010.

Abstract

To investigate the effects of respiration defects on the disease phenotypes, we generated trans-mitochondrial mice (mito-mice) by introducing a mutated G13997A mtDNA, which specifically induces respiratory complex I defects and metastatic potentials in mouse tumor cells. First, we obtained ES cells and chimeric mice containing the G13997A mtDNA, and then we generated mito-mice carrying the G13997A mtDNA via its female germ line transmission. The three-month-old mito-mice showed complex I defects and lactate overproduction, but showed no other phenotypes related to mitochondrial diseases or tumor formation, suggesting that aging or additional nuclear abnormalities are required for expression of other phenotypes.

Keywords: Somatic mtDNA mutation, Metastasis, mtDNA transfer, Trans-mitochondrial mito-mice