Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases
Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases
复制标题
极体基因组转移预防遗传性线粒体疾病的传播
DOI：
10.1016/j.cell.2014.04.042
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发表时间：
2014-06-19
期刊：
影响因子：
64.5
通讯作者：
Zhu, Jianhong
中科院分区：
文献类型：
--
作者：
Wang, Tian;Sha, Hongying;Zhu, Jianhong
遗传性mtDNA疾病通过母系传播并导致严重的表型。目前，这些疾病还没有有效的治疗方法或遗传筛查;然而，在患者和健康卵子之间转移核基因组以取代突变的mtDNA是有希望的。考虑到极体含有很少的线粒体，并且与卵母细胞共享相同的基因组物质，我们进行极体转移以防止mtDNA变体的传播。我们比较了不同类型的生殖系基因组转移，包括纺锤体染色体转移，原核转移，第一和第二极体转移，在小鼠中的效果。重建的胚胎支持正常受精并产生活的后代。重要的是，遗传分析证实，与其他程序的F1代相比，极体转移的F1代具有最小的供体mtDNA携带。此外，线粒体基因型在极体转移后的F2后代中保持稳定。我们的临床前模型表明，极体转移具有预防遗传性mtDNA疾病的巨大潜力。
Inherited mtDNA diseases transmit maternally and cause severe phenotypes. Currently, there is no effective therapy or genetic screens for these diseases; however, nuclear genome transfer between patients' and healthy eggs to replace mutant mtDNAs holds promises. Considering that a polar body contains few mitochondria and shares the same genomic material as an oocyte, we perform polar body transfer to prevent the transmission of mtDNA variants. We compare the effects of different types of germline genome transfer, including spindle-chromosome transfer, pronuclear transfer, and first and second polar body transfer, in mice. Reconstructed embryos support normal fertilization and produce live offspring. Importantly, genetic analysis confirms that the F1 generation from polar body transfer possesses minimal donor mtDNA carryover compared to the F1 generation from other procedures. Moreover, the mtDNA genotype remains stable in F2 progeny after polar body transfer. Our preclinical model demonstrates polar body transfer has great potential to prevent inherited mtDNA diseases.