Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer

Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer
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DOI:
10.1016/j.cell.2018.01.020
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发表时间:
2018-02-08
期刊:
影响因子:
64.5
通讯作者:
Sun, Qiang
Sun, Qiang
中科院分区:
生物学1区
文献类型:
--
作者:
Liu, Zhen;Cai, Yijun;Sun, Qiang

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遗传均一的非人灵长类动物的产生可能有助于建立灵长类生物学和生物医学研究的动物模型。在这项研究中,我们成功地克隆食蟹猴(Macaca fascicularis)的体细胞核移植(SCNT)。我们发现,注射H3K9me3去甲基化酶Kdm4d mRNA和组蛋白去乙酰化酶抑制剂阿司他丁A处理后的一个细胞阶段,SCNT大大提高囊胚发育和移植的SCNT胚胎在代孕猴的妊娠率。对于使用胎猴成纤维细胞的SCNT,在21个代理人中确认了6次妊娠,并产生了2个健康婴儿。对于使用成年猴卵丘细胞的SCNT,在42个代理人中确认了22次妊娠,并产生了2个短命的婴儿。在这两种情况下,遗传分析证实,猴子后代的核DNA和线粒体DNA分别来自核供体细胞和卵母细胞供体猴子。因此,利用胎儿成纤维细胞通过SCNT克隆猕猴是可行的。
Generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. In this study, we have successfully cloned cynomolgus monkeys (Macaca fascicularis) by somatic cell nuclear transfer (SCNT). We found that injection of H3K9me3 demethylase Kdm4d mRNA and treatment with histone deacetylase inhibitor trichostatin A at one-cell stage following SCNT greatly improved blastocyst development and pregnancy rate of transplanted SCNT embryos in surrogate monkeys. For SCNT using fetal monkey fibroblasts, 6 pregnancies were confirmed in 21 surrogates and yielded 2 healthy babies. For SCNT using adult monkey cumulus cells, 22 pregnancies were confirmed in 42 surrogates and yielded 2 babies that were short-lived. In both cases, genetic analyses confirmed that the nuclear DNA and mitochondria DNA of the monkey offspring originated from the nucleus donor cell and the oocyte donor monkey, respectively. Thus, cloning macaque monkeys by SCNT is feasible using fetal fibroblasts.