Open AccessCharacterization of a transgenic mouse model of chronic conditional platelet depletion
Author(s) -
Wuescher Leah M.,
Nishat Sharmeen,
Worth Randall G.
Publication year - 2019
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12255
Subject(s) - platelet , diphtheria toxin , hemostasis , immunology , antibody , platelet activation , genetically modified mouse , platelet factor 4 , transgene , biology , medicine , toxin , microbiology and biotechnology , biochemistry , gene
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 PF 4‐ DTR mouse model of conditional platelet depletion compared to antibody depletion. Methods We describe the ability of the PF 4‐ 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, PF 4‐ 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, PF 4‐ DTR mice showed similar phenotypes and should be considered an important tool for examining the impact of thrombocytopenia over longer periods of time.