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

doi:10.1016/j.bbrc.2015.12.006

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

Department of Oral Medicine

Research output: Contribution to journal › Article › peer-review

14 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 language	English
Pages (from-to)	761-767
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	469
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2015.12.006
Publication status	Published - 15 Jan 2016

Keywords

CRISPR/Cas9
Conditional knockout mouse
Esophageal cancer
Notch1
Transgenic mouse

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2015.12.006

Cite this

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

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.",

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AU - Sawangarun, Wanlada

AU - Katsube, Ken Ichi

AU - Kayamori, Kou

AU - Yamaguchi, Akira

AU - Sakamoto, Kei

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KW - Conditional knockout mouse

KW - Esophageal cancer

KW - Notch1

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

Abstract

Keywords

UN SDGs

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