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他莫昔芬诱导型Eomes(CreER)小鼠品系的构建与鉴定

Generation and characterization of a tamoxifen-inducible Eomes(CreER) mouse line.

作者信息

Pimeisl Inga-Marie, Tanriver Yakup, Daza Ray A, Vauti Franz, Hevner Robert F, Arnold Hans-Henning, Arnold Sebastian J

机构信息

University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany.

出版信息

Genesis. 2013 Oct;51(10):725-33. doi: 10.1002/dvg.22417. Epub 2013 Aug 30.

Abstract

Transgenic mouse lines expressing inducible forms of Cre-recombinase in a tissue-specific manner are powerful genetic tools for studying aspects of development and various processes in the adult. The T-box transcription factor eomesodermin (Eomes) plays critical roles for maintenance and differentiation of different pools of stem and progenitor cells from early embryonic stages to adulthood. These include trophoblast stem cells, epiblast cells during the generation of the primary germ layers, neurogenic intermediate progenitor cells in embryonic and adult cortical neurogenesis, and maturing natural killer and T cells. Here, we report on the generation and analysis of an Eomes(CreER) -targeted allele by placing the tamoxifen-activatable Cre-recombinase (CreER) under the control of the Eomes genomic locus. We demonstrate that CreER expression recapitulates endogenous Eomes transcription within different progenitor cell populations. Tamoxifen administration specifically labels Eomes-expressing cells and their progeny as demonstrated by crossing Eomes(CreER) animals to different Cre-inducible reporter strains. In summary, this novel Eomes(CreER) allele can be used as elegant genetic tool that allows to follow the fate of Eomes-positive cells and to genetically manipulate them in a temporal specific manner.

摘要

以组织特异性方式表达可诱导形式的Cre重组酶的转基因小鼠品系,是研究发育方面和成年期各种过程的强大遗传工具。T盒转录因子Eomesodermin(Eomes)在从早期胚胎阶段到成年期的不同干细胞和祖细胞群体的维持和分化中起着关键作用。这些细胞包括滋养层干细胞、原肠胚形成过程中的上胚层细胞、胚胎和成年皮质神经发生中的神经源性中间祖细胞,以及成熟的自然杀伤细胞和T细胞。在这里,我们报告了通过将他莫昔芬激活的Cre重组酶(CreER)置于Eomes基因组位点的控制下,生成和分析Eomes(CreER)靶向等位基因的情况。我们证明,CreER表达在不同祖细胞群体中重现了内源性Eomes转录。如将Eomes(CreER)动物与不同的Cre诱导报告菌株杂交所示,给予他莫昔芬可特异性标记表达Eomes的细胞及其后代。总之,这种新型的Eomes(CreER)等位基因可作为一种出色的遗传工具,用于追踪Eomes阳性细胞的命运,并以时间特异性方式对其进行基因操作。

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