Characterization of transgenic mice expressing cancer-associated variants of human NOTCH1 |
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Authors: | Berquam-Vrieze Katherine E Swing Deborah A Tessarollo Lino Dupuy Adam J |
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Institution: | Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. |
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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. |
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Keywords: | mouse models of cancer BAC recombineering BAC transgenesis |
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