Birth of parthenogenetic mice that can develop to adulthood
Birth of parthenogenetic mice that can develop to adulthood
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DOI：
10.1038/nature02402
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发表时间：
2004-04-22
期刊：
影响因子：
64.8
通讯作者：
Ogawa, H
中科院分区：
文献类型：
--
作者：
Kono, T;Obata, Y;Ogawa, H
只有哺乳动物放弃了孤雌生殖，这是一种仅由母体生殖细胞产生后代的手段。小鼠孤雌生殖胚胎在怀孕10天(1-4天)死亡。双亲繁殖是必要的，因为在配子发生过程中对基因组进行了双亲特有的表观遗传修饰(5-8)。这导致母本和父本等位基因印记基因的表达不平等(9)。然而，没有直接证据表明基因组印记是孤雌生殖发育的唯一障碍。在这里，我们展示了从包含两组单倍体母体基因组的重构卵母细胞中发育出一个可存活的孤雌生殖小鼠个体，这些基因组来自未生长的和完全发育的卵母细胞。这一发展是通过适当地表达Igf2和H19基因以及其他印记基因来实现的，使用H19基因(10)13kb碱基缺失的突变小鼠作为不生长的卵母细胞捐赠者。这种完整的发育与异常表达基因的显著减少有关。单亲动物发育到成年，具有繁殖后代的能力。这些结果表明，父亲的印记阻止了孤雌生殖，确保了父亲的贡献是后代的义务。
Only mammals have relinquished parthenogenesis, a means of producing descendants solely from maternal germ cells. Mouse parthenogenetic embryos die by day 10 of gestation(1-4). Bi-parental reproduction is necessary because of parent-specific epigenetic modification of the genome during gametogenesis(5-8). This leads to unequal expression of imprinted genes from the maternal and paternal alleles(9). However, there is no direct evidence that genomic imprinting is the only barrier to parthenogenetic development. Here we show the development of a viable parthenogenetic mouse individual from a reconstructed oocyte containing two haploid sets of maternal genome, derived from non-growing and fully grown oocytes. This development was made possible by the appropriate expression of the Igf2 and H19 genes with other imprinted genes, using mutant mice with a 13-kilobase deletion in the H19 gene(10) as non-growing oocytes donors. This full-term development is associated with a marked reduction in aberrantly expressed genes. The parthenote developed to adulthood with the ability to reproduce offspring. These results suggest that paternal imprinting prevents parthenogenesis, ensuring that the paternal contribution is obligatory for the descendant.