A facile one-step strategy for the generation of conditional knockout mice to explore the role of Notch1 in oroesophageal tumorigenesis.
A facile one-step strategy for the generation of conditional knockout mice to explore the role of Notch1 in oroesophageal tumorigenesis.
复制标题
一种简便的一步策略，用于生成条件敲除小鼠，以探索 Notch1 在口食管肿瘤发生中的作用。
DOI：
10.1016/j.bbrc.2015.12.006
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Sakamoto K
中科院分区：
文献类型：
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作者：
Mandasari M;Sawangarun W;Katsube K;Kayamori K;Yamaguchi A;Sakamoto K
NOTCH1在上皮分化和癌变中起重要作用。为了研究notch1失活对口食管上皮的影响，我们利用krt14启动子诱导靶向notch1和cas9的单导RNA表达的组合构建了条件敲除（cKO）小鼠。cKO小鼠表现出斑片状脱发和舌上皮中多个notch1阴性区域，表明异质敲除。cKO小鼠表现出对食管肿瘤发生的易感性，强调notch1是肿瘤抑制因子。我们的一步培育cKO小鼠的策略提供了一种多功能的方法来检测基因在体内的功能。
NOTCH1 plays an important role in epithelial differentiation and carcinogenesis. To investigate the impact ofNotch1inactivation in oroesophageal epithelium, we generated conditional knockout (cKO) mice, using a combined construct which induces the expression of single guide RNA targetingNotch1andCas9by theKRT14promoter. The cKO mice exhibited patchy hair loss and multiple NOTCH1-negative areas in the tongue epithelium, indicative of heterogeneous knockout. The cKO mice showed susceptibility to esophageal tumorigenesis, underscoringNotch1as a tumor suppressor. Our one-step strategy for generation of cKO mice provides a versatile method to examine a gene functionin vivo.