Novel platelet glycoprotein VI and CLEC-2 targeting strategies: studies in humanized mouse models

Drugs targeting platelets play an important role in preventing or treating thrombotic events, for example stroke and heart attack, thus increasing the life quality and expectancy of patients. This thesis investigated the role of a promising target for anti-platelet therapy, Glycoprotein (GP) VI, a platelet receptor. First, the work in this thesis used in vitro models of microfluidics to compare the effect of GPVI-blockade compared to other drugs. Second, in order to study GPVI’s function in the living organism as well as possible strategies to inhibit its function, this work made use of a mouse model humanized for this platelet receptor. In addition, this thesis presented a second mouse model humanized for another platelet receptor, CLEC-2, also considered a potential therapeutic target. Finally, this thesis provided key information to further develop therapeutics targeting GPVI and provided a first in vivo model to study human CLEC-2 in the living organism.