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首页> 外文期刊>Cell discovery. >Rapidly generating knockout mice from H19-Igf2 engineered androgenetic haploid embryonic stem cells
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Rapidly generating knockout mice from H19-Igf2 engineered androgenetic haploid embryonic stem cells

机译：从 H19-Igf2 工程雄激素单倍体胚胎干细胞快速生成敲除小鼠

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摘要

Haploid mammalian embryonic stem cells (ESCs) hold great promise for functional genetic studies and assisted reproduction. Recently, rodent androgenetic haploid ESCs (AG-haESCs) were generated from androgenetic blastocysts and functioned like sperm to produce viable offspring via the intracytoplasmic AG-haESCs injection into oocytes. However, the efficiency of this reproduction was very low. Most pups were growth-retarded and died shortly after birth, which is not practical for producing knockout animals. Further investigation suggested a possible link between the low birthrate and aberrant expression of imprinted genes. Here, we report the high-frequency generation of healthy, fertile mice from H19-Igf2 imprinting-locus modified AG-haESCs, which maintained normal paternal imprinting and pluripotency. Moreover, it is feasible to perform further genetic manipulations in these AG-haESCs. Our study provides a reliable and efficient tool to rapidly produce gene-modified mouse models and will benefit reproductive medicine in the future.
机译：单倍体哺乳动物胚胎干细胞（ESC）在功能基因研究和辅助生殖方面具有广阔的前景。最近，从雄激素性胚泡中产生了啮齿动物雄激素单倍体胚胎干细胞（AG-haESCs），并像精子一样发挥作用，通过向卵母细胞中注射细胞内AG-haESCs产生了后代。但是，这种再现的效率非常低。多数幼崽生长迟缓，出生后不久就死亡，这对生产基因敲除动物不切实际。进一步的研究表明低出生率和印迹基因的异常表达之间可能存在联系。在这里，我们报告了从H19-Igf2印迹基因座修饰的AG-haESCs产生的健康，可育小鼠的高频生成，该基因维持了正常的父系印迹和多能性。而且，在这些AG-haESC中进行进一步的遗传操作是可行的。我们的研究为快速产生基因修饰的小鼠模型提供了可靠且有效的工具，并将在未来使生殖医学受益。

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