| First Author | Mito T | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 2 | Pages | e55789 |
| PubMed ID | 23418460 | Mgi Jnum | J:199416 |
| Mgi Id | MGI:5502520 | Doi | 10.1371/journal.pone.0055789 |
| Citation | Mito T, et al. (2013) Mitochondrial DNA mutations in mutator mice confer respiration defects and B-cell lymphoma development. PLoS One 8(2):e55789 |
| abstractText | Mitochondrial DNA (mtDNA) mutator mice are proposed to express premature aging phenotypes including kyphosis and hair loss (alopecia) due to their carrying a nuclear-encoded mtDNA polymerase with a defective proofreading function, which causes accelerated accumulation of random mutations in mtDNA, resulting in expression of respiration defects. On the contrary, transmitochondrial mito-miceDelta carrying mtDNA with a large-scale deletion mutation (DeltamtDNA) also express respiration defects, but not express premature aging phenotypes. Here, we resolved this discrepancy by generating mtDNA mutator mice sharing the same C57BL/6J (B6J) nuclear background with that of mito-miceDelta. Expression patterns of premature aging phenotypes are very close, when we compared between homozygous mtDNA mutator mice carrying a B6J nuclear background and selected mito-miceDelta only carrying predominant amounts of DeltamtDNA, in their expression of significant respiration defects, kyphosis, and a short lifespan, but not the alopecia. Therefore, the apparent discrepancy in the presence and absence of premature aging phenotypes in mtDNA mutator mice and mito-miceDelta, respectively, is partly the result of differences in the nuclear background of mtDNA mutator mice and of the broad range of DeltamtDNA proportions of mito-miceDelta used in previous studies. We also provided direct evidence that mtDNA abnormalities in homozygous mtDNA mutator mice are responsible for respiration defects by demonstrating the co-transfer of mtDNA and respiration defects from mtDNA mutator mice into mtDNA-less (rho(0)) mouse cells. Moreover, heterozygous mtDNA mutator mice had a normal lifespan, but frequently developed B-cell lymphoma, suggesting that the mtDNA abnormalities in heterozygous mutator mice are not sufficient to induce a short lifespan and aging phenotypes, but are able to contribute to the B-cell lymphoma development during their prolonged lifespan. |
