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超越小鼠:用于研究早期哺乳动物发育和生物医学研究的非啮齿动物模型。

Beyond the mouse: non-rodent animal models for study of early mammalian development and biomedical research.

作者信息

Madeja Zofia E, Pawlak Piotr, Piliszek Anna

机构信息

Faculty of Veterinary Medicine and Animal Sciences, Poznan University of Life Sciences, Poznan, Poland.

出版信息

Int J Dev Biol. 2019;63(3-4-5):187-201. doi: 10.1387/ijdb.180414ap.

DOI:10.1387/ijdb.180414ap
PMID:31058296
Abstract

The preimplantation development of mammals generally follows the same plan. It starts with the formation of a totipotent zygote, and through consecutive cleavage divisions and differentiation events leads to blastocyst formation. However, the intervening events may differ between species. The regulation of these processes has been extensively studied in the mouse, which displays some unique features among eutherian mammals. Farm animals such as pigs, cattle, sheep and rabbits share several similarities with one another, and with the human developmental plan. These include the timing of epigenetic reprogramming, the moment of embryonic genome activation and the developmental time-frame. Recently, efficient techniques for genetic modification have been established for large domestic animals. Genome sequences and gene manipulation tools are now available for cattle, pigs, sheep and goats, and a larger number of genetically engineered livestock is now accessible for biomedical research. Yet, these animals still make up less than 0.5% of animals in research, mainly due to our inadequate knowledge of the processes responsible for pluripotency maintenance (to date no stable naïve embryonic stem cell lines have been established) and early development. In this review, we highlight our present knowledge of the key preimplantation events in the 3 non-rodent species which present the highest potential for biomedical research related to early embryonic development: cattle, which offer an excellent model to study human in vitro embryo development, pigs which emerge as models to study the long-term effects of gene-based therapies and rabbits, which in many aspects of embryology resemble the human.

摘要

哺乳动物的植入前发育通常遵循相同的模式。它始于全能合子的形成,并通过连续的卵裂和分化事件导致囊胚形成。然而,中间事件在不同物种之间可能有所不同。这些过程的调控在小鼠中得到了广泛研究,小鼠在真兽类哺乳动物中表现出一些独特的特征。猪、牛、羊和兔等家畜彼此之间有一些相似之处,并且与人类的发育模式也有相似之处。这些相似之处包括表观遗传重编程的时间、胚胎基因组激活的时刻以及发育时间框架。最近,已经为大型家畜建立了高效的基因编辑技术。现在有了牛、猪、羊和山羊的基因组序列和基因操作工具,并且有更多的基因工程家畜可用于生物医学研究。然而这些动物在研究中所占比例仍不到0.5%,主要是因为我们对负责多能性维持的过程了解不足(迄今为止尚未建立稳定的原始胚胎干细胞系)以及对早期发育了解不足。在这篇综述中,我们重点介绍了目前我们对三种非啮齿类动物植入前关键事件的了解,这些动物在与早期胚胎发育相关的生物医学研究中具有最高潜力:牛是研究人类体外胚胎发育的优秀模型;猪成为研究基因疗法长期效果的模型;兔在胚胎学的许多方面与人类相似。

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