Birth of mice produced by germ cell nuclear transfer

Birth of mice produced by germ cell nuclear transfer
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DOI:
10.1002/gene.20100
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发表时间:
2005-02-01
期刊:
影响因子:
1.5
通讯作者:
Ogura, A
Ogura, A
中科院分区:
生物学4区
文献类型:
--
作者:
Miki, H;Inoue, K;Ogura, A

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哺乳动物可以通过核移植进行克隆,这表明有可能对体细胞基因组进行重新编程,以支持其全面发育。然而,生殖细胞的发育可塑性很难评估,因为基因组印记,这是正常的胎儿发育所必需的,正在重置在这个阶段。在胚胎11.5天或更晚的时候,由原始生殖细胞(PGCs)产生的小鼠克隆在印迹擦除过程中发育不良,证实了印迹的异常影响。然而,这也可以解释为意味着,与体细胞不同,分化的生殖细胞的基因组不能完全重编程。我们使用较年轻的PGCs(10.5天),最终获得了4个足月胎儿。DNA甲基化分析表明,只有表现出正常印记的胚胎才能发育到足月。因此,生殖细胞分化并不是克隆的不可逾越的障碍,而且作为核移植后发育可塑性的决定因素,印迹状态比核供体细胞本身的起源更重要。(C)2005年Wiley-Liss,Inc.
That mammals can be cloned by nuclear transfer indicates that it is possible to reprogram the somatic cell genome to support full development. However, the developmental plasticity of germ cells is difficult to assess because genomic imprinting, which is essential for normal fetal development, is being reset at this stage. The anomalous influence of imprinting is corroborated by the poor development of mouse clones produced from primordial germ cells (PGCs) during imprinting erasure at embryonic day 11.5 or later. However, this can also be interpreted to mean that, unlike somatic cells, the genome of differentiated germ cells cannot be fully reprogrammed. We used younger PGCs (day 10.5) and eventually obtained four full-term fetuses. DNA methylation analyses showed that only embryos exhibiting normal imprinting developed to term. Thus, germ cell differentiation is not an insurmountable barrier to cloning, and imprinting status is more important than the origin of the nucleus donor cell per se as a determinant of developmental plasticity following nuclear transfer. (C) 2005 Wiley-Liss, Inc.