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

Masita Mandasari, Wanlada Sawangarun, Ken Ichi Katsube, Kou Kayamori, Akira Yamaguchi, Kei Sakamoto

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)761-767
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume469
Issue number3
DOIs
Publication statusPublished - 15 Jan 2016

Keywords

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

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