Characterization of a transgenic mouse model of chronic conditional platelet depletion

BACKGROUND: Platelets are widely recognized for their role in maintaining hemostasis. Recently, platelets have become appreciated for their varying roles in immunity, neuroprotection, and other physiological processes. While there are currently excellent methods to transiently deplete platelets and models of thrombocytopenia, studying the roles of platelets in chronic processes can be challenging. OBJECTIVE: Phenotypic characterization of the PF4‐DTR mouse model of conditional platelet depletion compared to antibody depletion. METHODS: We describe the ability of the PF4‐DTR mouse to maintain chronic platelet depletion, along with examining the bleeding phenotype compared to antibody‐mediated platelet depletion. RESULTS: Systemic administration of diphtheria toxin resulted in >99% platelet depletion that can be maintained for >2 weeks. When compared to an antibody depletion model, PF4‐DTR mice showed similar phenotypes when challenged with tail bleed and saphenous vein measurements of hemostasis. Mice depleted with diphtheria toxin were also able to undergo adoptive transfer of platelets. If the frequency and amount of diphtheria toxin is reduced, mice can be maintained at >40% depletion for >28 days, showing that this model is tunable. CONCLUSIONS: When compared to the gold standard of antibody‐mediated depletion, PF4‐DTR mice showed similar phenotypes and should be considered an important tool for examining the impact of thrombocytopenia over longer periods of time.