Mouse lymphomyeloid cells can function with significantly decreased expression levels of cytochrome c
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Cytochrome c is an indispensable electron carrier in the mitochondrial respiratory chain and also an important mediator of the internal pathway triggering apoptosis. Mice with a complete deficiency of the Cycs gene encoding the somatic cytochrome c die during the embryogenesis. Using the technology of LoxP-cre-dependent tissue-specific recombination, we obtained some mouse strains with significantly reduced expression of cytochrome c in certain cell types (“conditional genetic knockdown”). This knockdown was achieved by abrogation of the normal splicing of the Cycs locus pre-mRNA due to an additional acceptor site inside the stop-cassette neor. Previously, we observed embryonic lethality in homozygous mice with the same knockdown of cytochrome c in all cells of the organism. In the present work we studied two novel mouse strains with conditional knockdown of the Cycs gene in T lymphocytes and macrophages. Somewhat surprisingly, the mice of these two strains under normal conditions were not phenotypically different from the wild-type mice, either on the whole organism level or on the level of activity of individual target cells. Thus, the amount of cytochrome c in lymphomyeloid cells does not affect their development and normal functioning.
Key wordscytochrome c genetic knockdown T lymphocytes macrophages cre recombinase splicing
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- 9.Mufazalov, I. A., Kruglov, A. A., Efimov, G. A., Drutskaya, M. S., Penkov, D. N., Kuprash, D. V., and Nedospasov, S. A. (2011) Effects of mutation in the cytochrome c gene and of inhibitors of reactive oxygen species on the accelerated involution of the thymus in mice heterogeneous by the TNF/LT, Ros. Immunolog. Zh., 2, 112–120.Google Scholar
- 10.Mufazalov, I. A., Penkov, D. N., Chernyak, B. V., Pletyushkina, O. Yu., Vysokikh, M. Yu., Chertkova, R. V., Kirpichnikov, M. P., Dolgikh, D. A., Kuprash, D. V., Skulachev, V. P., and Nedospasov, S. A. (2009) Embryonal mouse fibroblasts with the K72W mutation in the gene of somatic cytochrome c: obtaining and characteristics, Mol. Biol. (Moscow), 43, 648–656.CrossRefGoogle Scholar
- 14.Shilov, E. S., Mufazalov, I. A., Shebzukhov, Yu. V., Zvartsev, R. V., Drutskaya, M. S., and Nedospasov, S. A. (2013) Conditional genetic knockdown of the mouse somatic cytochrome c in lymphomyelid cells, Ros. Immunol. Zh., 4, 361–371.Google Scholar
- 20.Lapuente-Brun, E., Moreno-Loshuertos, R., Acin-Perez, R., Latorre-Pellicer, A., Colas, C., Balsa, E., Perales-Clemente, E., Quiros, P., Calvo, E., Rodriguez-Hernandez, M. A., Navas, P., Cruz, R., Carracedo, A., Lopez-Otin, C., Perez-Martos, A., Fernandez-Silva, P., Fernandez-Vizarra, E., and Enriquez, J. A. (2013) Supercomplex assembly determines electron flux in the mitochondrial electron transport chain, Science, 340, 1567–1570.PubMedCrossRefGoogle Scholar