{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:56:30Z","timestamp":1787579790770,"version":"build-2736575974"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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 (\u2206mtDNA), but there is no direct experimental evidence for this. To determine whether \u2206mtDNA has the pathologic potential to induce multiple mitochondrial disease phenotypes, we used trans-mitochondrial mice with a heteroplasmic state of wild-type mtDNA and \u2206mtDNA (mito-mice\u2206). Late-stage embryos carrying \u226550% \u2206mtDNA 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 \u2206mtDNA load in the affected tissues, peripheral blood and liver, and they recovered from PS-like phenotypes. The proportion of \u2206mtDNA in various tissues of the surviving mito-mice\u2206 increased with time, and Kearns-Sayre syndrome\u2212like phenotypes were expressed when the proportion of \u2206mtDNA in various tissues reached &amp;gt;70\u201380%. Our model mouse study clearly showed that a single \u2206mtDNA was responsible for at least two distinct disease phenotypes at different ages and suggested that the level and dynamics of \u2206mtDNA load in affected tissues would be important for the onset and transition of mitochondrial disease phenotypes in mice.<\/jats:p>","DOI":"10.1534\/g3.113.007245","type":"journal-article","created":{"date-parts":[[2013,7,15]],"date-time":"2013-07-15T18:44:12Z","timestamp":1373913852000},"page":"1545-1552","source":"Crossref","is-referenced-by-count":19,"title":["Mitochondrial DNA with a Large-Scale Deletion Causes Two Distinct Mitochondrial Disease Phenotypes in Mice"],"prefix":"10.1093","volume":"3","author":[{"given":"Shun","family":"Katada","sequence":"first","affiliation":[{"name":"Graduate School of Life and Environmental Sciences , University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Mito","sequence":"additional","affiliation":[{"name":"Graduate School of Life and Environmental Sciences , University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Ogasawara","sequence":"additional","affiliation":[{"name":"Faculty of Life and Environmental Sciences , University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ichi","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Faculty of Life and Environmental Sciences , University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan"},{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS) , University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Nakada","sequence":"additional","affiliation":[{"name":"Graduate School of Life and Environmental Sciences , University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan"},{"name":"Faculty of Life and Environmental Sciences , University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,9,1]]},"reference":[{"key":"2023082207431195000_bib1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1365-2141.2008.07290.x","article-title":"Recent advances in the understanding of inherited sideroblastic anaemia.","volume":"143","author":"Camaschella","year":"2008","journal-title":"Br. 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