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Mouse Models for Platelet Production and Function

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Molecular and Cellular Biology of Platelet Formation

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Abstract

Highly polyploid, mature bone marrow megakaryocytes convert their cytoplasm into long protrusions (proplatelets) which extend into the lumen of a vessel in bone marrow sinusoids where so-called pre-platelets are released and final platelet shaping and sizing occurs in the bloodstream. Platelets never undergo firm adhesion in the circulation, and only at sites of vascular injury, the adhesion potential becomes evident. This is critical for the formation of a platelet plug which seals the vessel and limits excessive blood loss, but is also a key step in the pathogenesis of ischemic cardio- and cerebrovascular diseases which represent the leading causes of death and severe disability worldwide. Static as well as shear stress-dependent in vitro assays helped us to identify and better understand the role of proteins and pathways in platelet biogenesis and function. However, in vitro experiments only provide limited mechanistic information as they cannot completely mimic these complex processes. The generation of genetically modified mice and the availability of large-scale mouse knockout programs producing a continuous resource of targeted mutations in all protein-encoding genes has been a major step forward in order to investigate these processes under in vivo conditions. Furthermore, the establishment of multiple assays to analyze platelet production and function, in combination with improved imaging techniques, such as intravital two-photon microscopy, helped us to better understand the underlying mechanisms. This chapter summarizes the most important mouse models that contributed significantly to our current knowledge.

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Acknowledgments

Prof. Dr. Bernhard Nieswandt holds a Chair of Experimental Biomedicine at the University Clinic and Rudolf Virchow Center, Würzburg Germany. This work was supported by the Deutsche Forschungsgemeinschaft (SFB688) and the Rudolf Virchow Centre.

Dr. Markus Bender is supported by the Deutsche Forschungsgemeinschaft (DFG) as a group leader in the Emmy Noether program of the DFG (BE 5084/3-1).

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  1. Department of Experimental Biomedicine, University of Würzburg,University Hospital and Rudolf Virchow Center, Würzburg, Germany

    Markus Bender & Bernhard Nieswandt

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  1. Markus Bender
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  2. Bernhard Nieswandt
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Correspondence to Markus Bender .

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  1. Institute of Experimental Biomedicine I, University Hospital Würzburg, Würzburg, Germany

    Harald Schulze

  2. Vascular Biology Programm, Harvard Medical School, Boston, Massachusetts, USA

    Joseph Italiano

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Bender, M., Nieswandt, B. (2016). Mouse Models for Platelet Production and Function. In: Schulze, H., Italiano, J. (eds) Molecular and Cellular Biology of Platelet Formation. Springer, Cham. https://doi.org/10.1007/978-3-319-39562-3_11

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