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Genetics, Vol. 167, 1855-1861, August 2004, Copyright © 2004
doi:10.1534/genetics.103.021287
In Vivo Interaction Between Mitochondria Carrying mtDNAs From Different Mouse Species
Akitsugu Sato*,
,
Kazuto Nakada*,
,
Hiroshi Shitara,
Hiromichi Yonekawa and
Jun-Ichi Hayashi*,
,1
* Institute of Biological Sciences, University of Tsukuba, Ibaraki 305-8572, Japan
Center for Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki 305-8572, Japan
Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan
Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan
1 Corresponding author: Institute of Biological Sciences, University of Tsukuba, Ibaraki 305-8572, Japan.
E-mail: jih45{at}sakura.cc.tsukuba.ac.jp
Mitochondrial disease model mice, mitomice, were created using zygotes of B6mtspr strain mice carrying mitochondrial DNA (mtDNA) from Mus spretus as recipients of exogenous mitochondria carrying wild-type and a deletion mutant mtDNA (
mtDNA) of M. musculus domesticus. In these experiments, mtDNAs from different mouse species were used for identification of exo- and endogenous wild-type mtDNAs in the mitomice. Results showed transmission of exogenous mtDNA, but not exogenous wild-type mtDNA, of M. m. domesticus to following generations through the female germ line. Complete elimination of exogenous wild-type mtDNA would be due to stochastic segregation, whereas transmission of exogenous mtDNA would be due to its smaller size leading to a propagational advantage. Tissues in mitomice of the F3 generation carrying exogenous mtDNA showed protection from respiration defects until mtDNA accumulated predominantly. This protection from expression of mitochondrial dysfunction was attained with the help of endogenous wild-type mtDNA of M. spretus, since mitomice did not possess exogenous wild-type mtDNA of M. m. domesticus. These observations provide unambiguous evidence for the presence of interaction between exogenous mitochondria carrying mtDNA and endogenous mitochondria carrying M. spretus wild-type mtDNA.
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