A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In Vivo

Publication date: 9 May 2017
Source:Cell Reports, Volume 19, Issue 6
Author(s): Yu-Ping Yang, Haiting Ma, Alina Starchenko, Won Jae Huh, Wei Li, F. Edward Hickman, Qin Zhang, Jeffrey L. Franklin, Douglas P. Mortlock, Sabine Fuhrmann, Bruce D. Carter, Rebecca A. Ihrie, Robert J. Coffey
EGF receptor (EGFR) is a critical signaling node throughout life. However, it has not been possible to directly visualize endogenous Egfr in mice. Using CRISPR/Cas9 genome editing, we appended a fluorescent reporter to the C terminus of the Egfr. Homozygous reporter mice appear normal and EGFR signaling is intact in vitro and in vivo. We detect distinct patterns of Egfr expression in progenitor and differentiated compartments in embryonic and adult mice. Systemic delivery of EGF or amphiregulin results in markedly different patterns of Egfr internalization and trafficking in hepatocytes. In the normal intestine, Egfr localizes to the crypt rather than villus compartment, expression is higher in adjacent epithelium than in intestinal tumors, and following colonic injury expression appears in distinct cell populations in the stroma. This reporter, under control of its endogenous regulatory elements, enables in vivo monitoring of the dynamics of Egfr localization and trafficking in normal and disease states.

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Teaser

Yang et al. generate a chimeric protein reporter mouse that allows visualization of Egfr expression. Analysis with this mouse permits identification of neural stem cells and enables monitoring of Egfr localization dynamics and trafficking in vivo.


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