Mitochondrial gene replacement in primate offspring and embryonic stem cells.
Mitochondrial gene replacement in primate offspring and embryonic stem cells.
复制标题
灵长类动物后代和胚胎干细胞中的线粒体基因替代。
作者：
线粒体存在于所有真核细胞中，并含有自己的基因组 (mtDNA)。与受精时源自卵子和精子的核基因组不同，胚胎中的线粒体DNA几乎完全源自卵子，即源自母体。线粒体 DNA 突变导致多种仍无法治愈的人类疾病和失调。为了建立新治疗方法的临床前模型，我们在此证明，通过将纺锤体-染色体复合物从一个卵子转移到去核、线粒体丰富的卵子，可以有效地替换成熟非人灵长类卵母细胞中的线粒体基因组。经过线粒体替代的重建卵母细胞能够支持正常受精、胚胎发育并产生健康的后代。遗传分析证实，目前出生的三名婴儿的核DNA均来自纺锤体供体，而线粒体DNA则来自细胞质供体。在后代中没有检测到纺锤体供体 mtDNA 的贡献。这里显示的纺锤体替换是一种有效的方案，替换了新生成的胚胎干细胞系中全部线粒体。这种方法可能会提供一种生殖选择，以防止受影响家庭中 mtDNA 疾病的传播。
Mitochondria are found in all eukaryotic cells and contain their own genome (mtDNA). Unlike the nuclear genome which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo are derived almost exclusively from the egg, i.e. is of maternal origin. Mutations in mtDNA contribute to a diverse range of still incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature nonhuman primate oocytes by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors while mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.
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DOI：
10.1038/nrg1606
发表时间：
2005-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.1
作者：
Mitalipov, S. M.;Zhou, Q.;Wolf, D. P.
通讯作者：
Wolf, D. P.
影响因子：
4.2
作者：
Tsuboniwa, N;Morishita, R;Kaneda, Y
通讯作者：
Kaneda, Y
影响因子：
30.8
作者：
Cree, Lynsey M.;Samuels, David C.;Chinnery, Patrick F.
通讯作者：
Chinnery, Patrick F.
影响因子：
64.8
作者：
HOLT, IJ;HARDING, AE;MORGANHUGHES, JA
通讯作者：
MORGANHUGHES, JA