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.
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masita
authors.initials: M
authors.lastname: Mandasari
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Wanlada
authors.initials: W
authors.lastname: Sawangarun
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Department of Nursing Science, Faculty of Human Care, Tohto College of Health Sciences, Saitama, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Katsube
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kou
authors.initials: K
authors.lastname: Kayamori
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Oral Health Science Center, Tokyo Dental College, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: s-kei.mpa@tmd.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C497762:Notch1 protein, mouse; D051881:Receptor, Notch1
keywords: CRISPR/Cas9; Conditional knockout mouse; Esophageal cancer; Notch1; Transgenic mouse