Generation and characterization of mice for conditional inactivation of Zeb1

Generation and characterization of mice for conditional inactivation of Zeb1
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DOI:
10.1002/dvg.23024
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发表时间:
2017-04-01
期刊:
影响因子:
1.5
通讯作者:
Stemmler, Marc P.
Stemmler, Marc P.
中科院分区:
生物学4区
文献类型:
--
作者:
Brabletz, Simone;Losada, Maria Lasierra;Stemmler, Marc P.

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多锌指转录因子ZEB 1在哺乳动物发育和肿瘤发生的各个方面起着至关重要的作用。在人类肿瘤中研究得最好的是,ZEB 1激活了胚胎来源的上皮-间质转化(EMT)程序。EMT的异常激活赋予了具有干细胞特性的侵袭性转移表型和对放射和化学疗法的抗性。虽然ZEB 1在肿瘤进展中具有非常重要的功能,但对其在生理背景以及发育和稳态过程中的作用知之甚少。我们描述了一代Zeb 1(flox/flox)小鼠携带有针对性的突变条件Zeb 1基因失活,并表明纯合子Zeb 1-耗尽在种系中的表型类似于传统的Zeb 1基因敲除。
The multizinc finger containing transcription factor ZEB1 plays crucial roles during various aspects of mammalian development and tumorigenesis. Best studied in human tumors, ZEB1 is activating the embryo-derived program of epithelial-mesenchymal transition (EMT). The aberrant activation of EMT confers an invasive metastasizing phenotype with acquisition of stem cell properties and resistance to radio- and chemotherapy. Although ZEB1 has very important functions in tumor progression, not much is known about its role in physiological contexts and during development and homeostasis. We describe the generation of Zeb1(flox/flox) mice carrying a targeted mutation for conditional Zeb1 gene inactivation and show that homozygous Zeb1-depletion in the germline results in a phenotype similar to the conventional Zeb1 knockout.