hematopoietic system
N |
• homozygotes exhibit normal peripheral platelet counts relative to control littermates
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• expression levels of integrin beta1 are decreased by ~30% whereas expression of alpha5 and alpha6 is significantly increased in mutant platelets relative to control platelets
• in contrast, expression levels of integrin beta3, GPVI (activating platelet collagen receptor), or the GPIb-V-IX complex, remain normal
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• aggregation of mutant platelets in reponse to fibrillar type I collagen is significantly delayed, esp. at low collagen concentrations; however, dose-response and maximum aggregation are similar to those in control platelets
• mutant platelets display normal aggregation in response to induction by the GPVI-specific agonist collagen-related peptide (CRP), ADP or thrombin
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• aggregation of mutant platelets in response to 500 ug/ml of enzymatically digested soluble collagen is essentially abolished, unlike in control platelets where robust aggregation is already evident at 5 ug/ml
• under static conditions, mutant platelets display normal adhesion in reponse to fibrillar collagen; however, blocking the major collagen-binding site on GPVI by JAQ1-Fab fragments abrogates adhesion of mutant platelets, whereas adhesion of control platelets remains relatively unchanged
• under static conditions, mutant platelets fail to adhere to soluble collagen in the presence or absence of JAQ1-Fab fragments, unlike control platelets which adhere in the absence, but not in the presence of JAQ1-Fab fragments
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homeostasis/metabolism
N |
• homozygotes are viable, fertile, anatomically normal and display normal tail bleeding times relative to control littermates
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• expression levels of integrin beta1 are decreased by ~30% whereas expression of alpha5 and alpha6 is significantly increased in mutant platelets relative to control platelets
• in contrast, expression levels of integrin beta3, GPVI (activating platelet collagen receptor), or the GPIb-V-IX complex, remain normal
|
• aggregation of mutant platelets in reponse to fibrillar type I collagen is significantly delayed, esp. at low collagen concentrations; however, dose-response and maximum aggregation are similar to those in control platelets
• mutant platelets display normal aggregation in response to induction by the GPVI-specific agonist collagen-related peptide (CRP), ADP or thrombin
|
• aggregation of mutant platelets in response to 500 ug/ml of enzymatically digested soluble collagen is essentially abolished, unlike in control platelets where robust aggregation is already evident at 5 ug/ml
• under static conditions, mutant platelets display normal adhesion in reponse to fibrillar collagen; however, blocking the major collagen-binding site on GPVI by JAQ1-Fab fragments abrogates adhesion of mutant platelets, whereas adhesion of control platelets remains relatively unchanged
• under static conditions, mutant platelets fail to adhere to soluble collagen in the presence or absence of JAQ1-Fab fragments, unlike control platelets which adhere in the absence, but not in the presence of JAQ1-Fab fragments
|