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Generation of genetically modified mice by oocyte injection of androgenetic haploid embryonic stem cells

机译：通过卵母细胞注射雄激素单倍体胚胎干细胞产生转基因小鼠

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Haploid cells are amenable for genetic analysis. Recent success in the derivation of mouse haploid embryonic stem cells (haESCs) via parthenogenesis has enabled genetic screening in mammalian cells. However, successful generation of live animals from these haESCs, which is needed to extend the genetic analysis to the organism level, has not been achieved. Here, we report the derivation of haESCs from androgenetic blastocysts. These cells, designated as AG-haESCs, partially maintain paternal imprints, express classical ESC pluripotency markers, and contribute to various tissues, including the germline, upon injection into diploid blastocysts. Strikingly, live mice can be obtained upon injection of AG-haESCs into MII oocytes, and these mice bear haESC-carried genetic traits and develop into fertile adults. Furthermore, gene targeting via homologous recombination is feasible in the AG-haESCs. Our results demonstrate that AG-haESCs can be used as a genetically tractable fertilization agent for the production of live animals via injection into oocytes. PaperClip
机译：单倍体细胞适合遗传分析。通过孤雌生殖衍生小鼠单倍体胚胎干细胞（haESCs）的最新成功使哺乳动物细胞中的遗传筛选成为可能。但是，尚未实现从这些haESC成功产生活动物，这需要将遗传分析扩展到生物体水平。在这里，我们报道了从雄激素性胚泡衍生出的胚胎干细胞。这些细胞被称为AG-haESCs，部分维持父系印记，表达经典的ESC多能性标记，并在注入二倍体胚泡后对包括生殖系在内的各种组织有贡献。引人注目的是，将AG-haESCs注射到MII卵母细胞中可以获得活体小鼠，这些小鼠具有haESC携带的遗传特征并发育成可育的成年动物。此外，在AG-haESC中通过同源重组的基因靶向是可行的。我们的结果表明，AG-haESCs可以用作遗传可控的受精剂，通过注入卵母细胞来生产活体动物。回形针

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