Analysis Tools
mortality/aging
| N |
• mice are viable and survive >6 months with no overt signs of ill-health or spontaneous bleeding
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hematopoietic system
| N |
• platelet counts in peripheral blood are similar to those in wild-type controls
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• red blood cells are only slightly reduced in peripheral blood
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• some mice exhibit variable presence of acanthocytes in blood smears
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• mice display significant leukocytosis in peripheral blood
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• integrin alphaIIbbeta3-mediated platelet spreading on immobilized fibrinogen is significantly reduced relative to wild-type platelets
• under high doses of thrombin, mutant platelets fail to support thrombin-induced clot retraction of platelet-rich plasma, unlike wild-type platelets
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• integrin alphaIIbbeta3 activation on mutant platelets is totally inhibited upon stimulation with ADP (20 umol/L) and partially but significantly inhibited (~50%) in response to protease-activated receptor 4 (PAR-4) agonist peptide (AYPGKF, 150 umol/L) or collagen-related peptide (2 ug/mL)
• however, P-selectin translocation to the platelet surface in response to stimulation with PAR-4 agonist peptide or collagen-related peptide is normal
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• mutant platelets display insignificant aggregation in response to ADP and only a weak response to U46619 relative to wild-type cells
• notably, partial aggregation of mutant platelets is noted in response to collagen and thrombin
• in an in vitro thrombus formation assay under flow conditions, whole blood drawn from mutant mice shows markedly reduced platelet adhesion and severely inhibited aggregation relative to wild-type blood
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homeostasis/metabolism
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• integrin alphaIIbbeta3-mediated platelet spreading on immobilized fibrinogen is significantly reduced relative to wild-type platelets
• under high doses of thrombin, mutant platelets fail to support thrombin-induced clot retraction of platelet-rich plasma, unlike wild-type platelets
|
|
• integrin alphaIIbbeta3 activation on mutant platelets is totally inhibited upon stimulation with ADP (20 umol/L) and partially but significantly inhibited (~50%) in response to protease-activated receptor 4 (PAR-4) agonist peptide (AYPGKF, 150 umol/L) or collagen-related peptide (2 ug/mL)
• however, P-selectin translocation to the platelet surface in response to stimulation with PAR-4 agonist peptide or collagen-related peptide is normal
|
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• mutant platelets display insignificant aggregation in response to ADP and only a weak response to U46619 relative to wild-type cells
• notably, partial aggregation of mutant platelets is noted in response to collagen and thrombin
• in an in vitro thrombus formation assay under flow conditions, whole blood drawn from mutant mice shows markedly reduced platelet adhesion and severely inhibited aggregation relative to wild-type blood
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• in a FeCl3-induced arterial thrombosis model, mice fail to exhibit carotid artery occlusion within the testing period (45 min), unlike wild-type mice which form stable occlusion within 15 min of vascular injury
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• in a tail bleeding assay, mice exhibit a significantly prolonged bleeding time (>600 s) relative to wild-type controls (211 +/- 126 s)
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immune system
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• mice display significant leukocytosis in peripheral blood
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