title: Characterization of transgenic mice expressing cancer-associated variants of human NOTCH1.
abstract: The Notch1 receptor plays a critical role in cell fate decisions during development. Activation of Notch signaling has been implicated in several types of cancer, particularly T-cell acute lymphoblastic leukemia (T-ALL). Consequently, several transgenic mouse strains have been made to study the role of Notch1 in T-ALL. However, the existing Notch1 transgenic lines mimic a translocation event found in only ∼1% of T-ALL cases. Here we describe three novel NOTCH1 transgenic mouse strains that have Cre-inducible expression of the entire human NOTCH1 locus, each possessing a common mutation found in T-ALL. Unlike existing Notch1 transgenic strains, these NOTCH1 transgenic strains express full-length receptors from an endogenous human promoter that should be susceptible to a number of Notch antagonists that have recently been developed. These strains will allow researchers to modulate Notch signaling to study both normal development and cancer biology.
authors: Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors: Katherine E
authors: KE
authors: Berquam-Vrieze
authors: Deborah A
authors: DA
authors: Swing
authors: Lino
authors: L
authors: Tessarollo
authors: Adam J
authors: AJ
authors: Dupuy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1