Loss of PIKFyve Kinase Function Driven by Platelet Factor 4 Promoter Results in Platelet Lysosomal Storage Defects and Infiltration of Multiple Organs with Vacuolated Macrophages
November 2011
in “
Blood
”
Studysummary This study found that selective deletion of PIKFyve kinase using a PF4 promoter in mice led to defective platelet lysosome biogenesis and a prothrombotic effect, with unexpected macrophage infiltration in multiple organs.
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The study investigated the effects of PIKFyve kinase deletion in platelets and megakaryocytes using a PF4 promoter-driven Cre recombinase in mice. The PIKFyvefl/fl PF4 Cre+ mice exhibited a pleomorphic phenotype, including dorsal hair loss, weight gain due to body swelling, and infiltration of multiple organs with vacuolated macrophages. Despite normal platelet counts, these mice showed increased basal lysosomal enzyme activity and a prothrombotic tendency, forming occluding thrombi faster than controls. The findings suggested that PIKFyve plays a role in platelet lysosome biogenesis and that PF4 Cre expression is not limited to megakaryocytes and platelets, highlighting potential issues with the PF4 Cre transgenic model.
