Gene targeting: techniques and applications to transplantation.

Gene targeting: techniques and applications to transplantation.
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基因靶向:移植技术和应用。

DOI:
10.1097/00007890-199711150-00001
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发表时间:
1997
期刊:
影响因子:
6.2
通讯作者:
M. J. Dallman
M. J. Dallman
中科院分区:
医学2区
文献类型:
--
作者:
Andrew C.G. Porter;M. J. Dallman

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20 世纪 80 年代中期,对活细胞基因组进行确定突变的方法被证明适用于哺乳动物细胞。这些方法后来被称为基因打靶,并很快与操纵全能小鼠胚胎干 (ES*) 细胞的技术相结合,使研究人员能够在试管中培育出基因变化纯合的小鼠。这种靶向小鼠可以表现出表型,提供有关基因功能的有价值的信息,或者可以作为人类遗传疾病的模型。这项强大的技术已经对广泛的生物学科产生了巨大影响。迄今为止,大多数靶向实验都涉及破坏靶基因,但创建微妙的、有条件的或组织特异性突变的方法已经开发出来,并且可能会变得越来越有用。未来,基因打靶很可能用于对人类体干细胞和来自小鼠以外的动物(例如猪或羊)的ES细胞进行基因修饰,分别对自体移植和异种移植产生重大影响。我们在此简短概述中的目的是调查已建立的和新兴的基因靶向方法、它们在理解移植物排斥方面的用途以及在临床移植中的潜在应用。为了更广泛地讨论这些技术及其应用,读者可以参考其他评论 (1-5)。
In the mid-1980s, methods for making defined mutations to the genome of living cells were shown to be applicable in mammalian cells. These methods became known as gene targeting and were soon combined with techniques for manipulating totipotent mouse embryonic stem (ES*) cells, allowing researchers to generate mice homozygous for genetic changes that had been engineered in the test tube. Such targeted mice can display phenotypes that provide valuable information on gene function or can serve as models of human genetic disease. This powerful technology has already had a huge impact on a wide spectrum of biological disciplines. To date, most targeting experiments have involved disruption of the target gene, but methods for the creation of subtle, conditional, or tissue-specific mutations have been developed and are likely to become increasingly useful. Further in the future, gene targeting may well be used for the genetic modification of human somatic stem cells and ES cells from animals other than mice (eg, pig or sheep) with major implications for autologous transplantation and xenotransplantaion, respectively. Our purpose in this brief overview is to survey established and emerging gene targeting methods, their use in understanding graft rejection, and potential applications in clinical transplantation. For a wider discussion of the techniques and their applications, the reader is referred to other reviews (1-5).
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