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

Cell Reports
Yu-Ping YangRobert J Coffey

Abstract

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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Citations

Nov 11, 2017·Molecular Oncology·Sara SigismundLetizia Lanzetti
Nov 5, 2019·Journal of the American Society of Nephrology : JASN·Eirini KefaloyianniAndreas Herrlich
May 15, 2021·Cellular and Molecular Gastroenterology and Hepatology·H NiitsuR J Coffey
Feb 20, 2021·Annual Review of Biochemistry·Mark von Zastrow, Alexander Sorkin
Aug 6, 2021·Frontiers in Cell and Developmental Biology·Helen E AbudThierry Jardé
Jan 2, 2021·Cell Regeneration·Guoli ZhuRongwen Xi

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