@article{oai:tsukuba.repo.nii.ac.jp:00029416,
 author = {林, 純一 and 中田, 和人 and Katada, Shun and Mito, Takayuki and Ogasawara, Emi and Hayashi, Jun-Ichi and Nakada, Kazuto},
 issue = {9},
 journal = {G3: Genes, Genomes, Genetics},
 month = {Sep},
 note = {Studies in patients have suggested that the clinical phenotypes of some mitochondrial diseases might transit from one disease to another (e.g., Pearson syndrome [PS] to Kearns-Sayre syndrome) in single individuals carrying mitochondrial (mt) DNA with a common deletion (∆mtDNA), but there is no direct experimental evidence for this. To determine whether ∆mtDNA has the pathologic potential to induce multiple mitochondrial disease phenotypes, we used trans-mitochondrial mice with a heteroplasmic state of wild-type mtDNA and ∆mtDNA (mito-mice∆). Late-stage embryos carrying ≥50% ∆mtDNA showed abnormal hematopoiesis and iron metabolism in livers that were partly similar to PS (PS-like phenotypes), although they did not express sideroblastic anemia that is a typical symptom of PS. More than half of the neonates with PS-like phenotypes died by 1 month after birth, whereas the rest showed a decrease of ∆mtDNA load in the affected tissues, peripheral blood and liver, and they recovered from PS-like phenotypes. The proportion of ∆mtDNA in various tissues of the surviving mito-mice∆ increased with time, and Kearns-Sayre syndrome−like phenotypes were expressed when the proportion of ∆mtDNA in various tissues reached >70–80%. Our model mouse study clearly showed that a single ∆mtDNA was responsible for at least two distinct disease phenotypes at different ages and suggested that the level and dynamics of ∆mtDNA load in affected tissues would be important for the onset and transition of mitochondrial disease phenotypes in mice.},
 pages = {1545--1552},
 title = {Mitochondrial DNA with a Large-Scale Deletion Causes Two Distinct Mitochondrial Disease Phenotypes in Mice},
 volume = {3},
 year = {2013}
}