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

The study investigated the role of PIKFyve kinase in platelet function by engineering mice to lack PIKFyve specifically in platelets and megakaryocytes. These PIKFyve-deficient mice exhibited a pleomorphic phenotype, including dorsal hair loss and significant weight gain due to the infiltration of vacuolated macrophages in multiple organs. 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 is crucial for platelet lysosome biogenesis and that the PF4 promoter-driven Cre expression affected more than just megakaryocytes and platelets, leading to macrophage infiltration. The study also raised concerns about the specificity of the PF4 Cre transgenic model used in research.