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Genetics, Vol. 155, 301-307, May 2000, Copyright © 2000

Complete Repopulation of Mouse Mitochondrial DNA-less Cells With Rat Mitochondrial DNA Restores Mitochondrial Translation but Not Mitochondrial Respiratory Function

Makiko Yamaokaa, Kotoyo Isobea, Hiroshi Shitaraa,c, Hiromichi Yonekawac, Shigeaki Miyabayashid, and Jun-Ichi Hayashia,b
a Institute of Biological Sciences, University of Tsukuba, Ibaraki 305-8572, Japan,
b Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan,
c Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan
d Department of Pediatrics, Tohoku University School of Medicine, Sendai 980-8574, Japan

Corresponding author: Jun-Ichi Hayashi, Institute of Biological Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan., jih45{at}sakura.cc.tsukuba.ac.jp (E-mail)

Communicating editor: N. TAKAHATA

By the fusion of mtDNA-less ({rho}0) cells of Mus musculus domesticus with platelets from different species, mtDNA repopulated cybrids were obtained for finding the mtDNA species that could induce mitochondrial abnormalities. Expression of mitochondrial dysfunction might be expected in these cybrids due to incompatibility between nuclear and mitochondrial genomes from different species. The results showed that mouse {rho}0 cells could receive mtDNA from a different mouse species, M. spretus, or even mtDNA from the rat, Rattus norvegicus, and that the introduced rat mtDNA, but not M. spretus mtDNA, caused mitochondrial dysfunction, even though rat mtDNA could restore normal mitochondrial translation in the cybrids. Considering that mitochondrial respiratory complexes consist of nuclear DNA- and mtDNA-coded polypeptides, these observations suggest that the nuclear and mitochondrial interactions required for replication, transcription, and translation of introduced rat mtDNA must be less stringently controlled than those required for formation of normal respiratory complexes. As no procedure for introduction of mutagenized mouse mtDNA into living cells has yet been established, these findings provide important insights into generating mtDNA-knockout mice.




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