Heteroplasmy of mouse mtDNA is genetically unstable and results in altered behavior and cognition.
Heteroplasmy of mouse mtDNA is genetically unstable and results in altered behavior and cognition.
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DOI：
10.1016/j.cell.2012.09.004
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发表时间：
2012-10-12
期刊：
影响因子：
64.5
通讯作者：
Wallace DC
中科院分区：
文献类型：
--
作者：
Sharpley MS;Marciniak C;Eckel-Mahan K;McManus M;Crimi M;Waymire K;Lin CS;Masubuchi S;Friend N;Koike M;Chalkia D;MacGregor G;Sassone-Corsi P;Wallace DC
线粒体DNA的母系遗传是大多数动物的规律，但这种模式的原因尚不清楚。为了研究压倒性单亲遗传的后果，我们产生了含有NZB和129 S6 mtDNA的混合物（异质性）的小鼠，在存在同源C57 BL/6 J核背景的情况下。对这两种mtDNA在随后的母系世代中的分离分析表明，NZB mtDNA的比例优先降低。最终，这种分离过程产生了NZB-129异质小鼠和它们的NZB或129 mtDNA同质小鼠。这三个线粒体DNA系的表型比较表明，NZB-129异质性小鼠，但没有同质性对应，减少活动，食物摄入，呼吸交换率;加重应激反应;和认知障碍。因此，两种正常但不同的小鼠mtDNA的混合物可能是遗传不稳定的，并可能产生不利的生理效应，这些因素可能解释mtDNA的单亲遗传的优势。
Maternal inheritance of mtDNA is the rule in most animals, but the reasons for this pattern remain unclear. To investigate the consequence of overriding uniparental inheritance, we generated mice containing an admixture (heteroplasmy) of NZB and 129S6 mtDNAs in the presence of a congenic C57BL/6J nuclear background. Analysis of the segregation of the two mtDNAs across subsequent maternal generations revealed that proportion of NZB mtDNA was preferentially reduced. Ultimately, this segregation process produced NZB-129 heteroplasmic mice and their NZB or 129 mtDNA homo-plasmic counterparts. Phenotypic comparison of these three mtDNA lines demonstrated that the NZB-129 heteroplasmic mice, but neither homoplasmic counterpart, had reduced activity, food intake, respiratory exchange ratio; accentuated stress response; and cognitive impairment. Therefore, admixture of two normal but different mouse mtDNAs can be genetically unstable and can produce adverse physiological effects, factors that may explain the advantage of uniparental inheritance of mtDNA.
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影响因子：
56.9
作者：
Fan, Weiwei;Waymire, Katrina G.;Wallace, Douglas C.
通讯作者：
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影响因子：
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