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

Edited by Angel Nebreda

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

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

a Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan

b Japan Society for the Promotion of Science (JSPS), 8 Ichiban-cho, Chiyoda-ku, Tokyo 102-8472, Japan

c Laboratory for Transgenic Technology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

d Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan

Corresponding author. Fax: +81 298536650.

1 Both authors contributed equally to this study.

PII: S0014-5793(10)00610-1

doi:10.1016/j.febslet.2010.07.048