Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic G13997A mtDNA from highly metastatic lung carcinoma cells.
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.
Yokota
Mutsumi
M
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Shitara
Hiroshi
H
Hashizume
Osamu
O
Ishikawa
Kaori
K
Nakada
Kazuto
K
Ishii
Rie
R
Taya
Choji
C
Takenaga
Keizo
K
Yonekawa
Hiromichi
H
Hayashi
Jun-Ichi
J
D000367:Age Factors; D000375:Aging / Q000235:genetics; D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002678:Chimera; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D053595:Embryonic Stem Cells; D005260:Female; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics
D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm