Characterization of a transgenic mouse model of chronic conditional platelet depletion
Abstract 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 platel...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12255 |
| _version_ | 1797709473580580864 |
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| author | Leah M. Wuescher Sharmeen Nishat Randall G. Worth |
| author_facet | Leah M. Wuescher Sharmeen Nishat Randall G. Worth |
| author_sort | Leah M. Wuescher |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T06:37:03Z |
| format | Article |
| id | doaj.art-64ff99c0f4254d60a1abebd65a6b7afd |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T06:37:03Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-64ff99c0f4254d60a1abebd65a6b7afd2023-09-03T01:13:49ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792019-10-013470471210.1002/rth2.12255Characterization of a transgenic mouse model of chronic conditional platelet depletionLeah M. Wuescher0Sharmeen Nishat1Randall G. Worth2Department of Medical Microbiology and Immunology University of Toledo College of Medicine and Life Sciences Toledo OhioDepartment of Medical Microbiology and Immunology University of Toledo College of Medicine and Life Sciences Toledo OhioDepartment of Medical Microbiology and Immunology University of Toledo College of Medicine and Life Sciences Toledo OhioAbstract 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.https://doi.org/10.1002/rth2.12255adoptive transferblood plateletsdiphtheria toxinmicethrombocytopenia |
| spellingShingle | Leah M. Wuescher Sharmeen Nishat Randall G. Worth Characterization of a transgenic mouse model of chronic conditional platelet depletion Research and Practice in Thrombosis and Haemostasis adoptive transfer blood platelets diphtheria toxin mice thrombocytopenia |
| title | Characterization of a transgenic mouse model of chronic conditional platelet depletion |
| title_full | Characterization of a transgenic mouse model of chronic conditional platelet depletion |
| title_fullStr | Characterization of a transgenic mouse model of chronic conditional platelet depletion |
| title_full_unstemmed | Characterization of a transgenic mouse model of chronic conditional platelet depletion |
| title_short | Characterization of a transgenic mouse model of chronic conditional platelet depletion |
| title_sort | characterization of a transgenic mouse model of chronic conditional platelet depletion |
| topic | adoptive transfer blood platelets diphtheria toxin mice thrombocytopenia |
| url | https://doi.org/10.1002/rth2.12255 |
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