Dysfunctional platelet membrane receptors: From humans to mice

The Room Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
Thrombosis and Haemostasis (Impact Factor: 5.76). 10/2004; 92(3):478-85. DOI: 10.1267/THRO04090478
Source: PubMed

ABSTRACT Insights into hemostasis and thrombosis have historically benefited from the astute diagnosis of human bleeding and thrombotic disorders followed by decades of careful biochemical characterization. This work has set the stage for the development of a number of mouse models of hemostasis and thrombosis generated by gene targeting strategies in the mouse genome. The utility of these models is the in depth analysis that can be performed on the precise molecular interactions that support hemostasis and thrombosis along with efficacy testing of various therapeutic strategies. Already the mouse has proven to be an excellent model of the processes that support hemostasis and thrombosis in the human vasculature. A brief summary of the salient phenotypes from knockout mice missing key platelet receptors is presented, including the glycoprotein (GP) Ib-IX-V and GP IIb/IIIa (alphaIIb/beta3) receptors; the collagen receptors, GP VI and alpha2/beta1; the protease activated receptors (PARs); and the purinergic receptors, P2Y(1) and P2Y(12). A few differences exist between mouse and human platelets and where appropriate those will be highlighted in this review. Concluding remarks focus on the importance of understanding the power and limitations of various in vitro, ex vivo and in vivo models currently being used and the impact of the mouse strain on the described platelet phenotype.

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    • "We and others, by using large animal models of thrombosis, have supported the hypothesis that vessel wall-derived TF is a primary contributor to arterial thrombus formation and propagation, yet, blood-borne TF may also contribute depending on the triggering lesion and the shear rate [23] [24]. Besides all this, an accurate in-depth determination of the mouse haemostatic system (i.e., coagulation and fibrinolytic systems, platelet structure, and platelet receptor/enzyme system) is still lacking, as nicely reviewed by Tsakiris et al, [25] and Ware [26], and species-related differences between rodents and humans should also be considered before interpreting the data. For instance, platelet counts in mice on average are four times those of humans and platelets are only approximately one half the volume of human platelets. "
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