A facile one-step strategy for the generation of conditional knockout mice to explore the role of Notch1 in oroesophageal tumorigenesis

作者：Mandasari Masita; Sawangarun Wanlada; Katsube Ken ichi; Kayamori Kou; Yamaguchi Akira; Sakamoto Kei^*

来源：Biochemical and Biophysical Research Communications, 2016, 469(3): 761-767.

DOI：10.1016/j.bbrc.2015.12.006

• CRISPR/Cas9
• Transgenic mouse
• Conditional knockout mouse
• Notch1
• Esophageal cancer

NOTCH1 plays an important role in epithelial differentiation and carcinogenesis. To investigate the impact of Notch1 inactivation in oroesophageal epithelium, we generated conditional knockout (cKO) mice, using a combined construct which induces the expression of single guide RNA targeting Notch1 and Cas9 by the KRT14 promoter. 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, underscoring Notch1 as a tumor suppressor. Our one-step strategy for generation of cKO mice provides a versatile method to examine a gene function in vivo.

• 出版日期2016-1-15