Characterization of transgenic mice expressing cancer-associated variants of human NOTCH1

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 anendogenous 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 bothnormal development and cancer biology. genesis 50:112–118, 2012. © 2011 Wiley Periodicals, Inc.