Open access
CRISPR/Cas9-mediated loss of FERMT3 reveals kindlin-3–independent neutrophil activity in LAD-III
Steven D. S. Webbers
Felipe Rojas-Rodriguez
Angela A. F. Gankema
Imran Khan
J. Geissler
A. Tool
Rupert Oellinger
R. van Bruggen
T. V. van Dam
Susanna C. Fagerholm
Markus Moser
T. W. Kuijpers
Medicine
Abstract
Mutations in FERMT3 cause LAD-III by impairing integrin function in neutrophils. Using CRISPR/Cas9, we generated FERMT3 KO cultured neutrophils with normal in vitro granulopoiesis, transcriptomic profiles, and recapitulated defective zymosan-induced ROS production. Basal adhesion and chemotaxis were reduced, whereas stimulus-induced integrin activity remained largely intact, suggesting kindlin-3–independent neutrophil activity.