Analysis Tools
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• platelets exhibit decreased retraction after thrombin activation compared to wild-type platelets
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• platelets exhibit decreased retraction after thrombin activation compared to wild-type platelets
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• markedly prolonged tail-bleeding times
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• moderately reduced platelet count
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• litters of 2-6 mice
• fewer than 35% double homozygotes
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• blood filled lymphatics in the intestine
• more pronounced than in Clec1btm1.1Arte single homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• decreased platelet life span in vivo resulting in increased turnover
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• moderate decrease following activation with integrin alpha2bbeta3
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• at low agonist concentrations (thromboxane A2 analog U46619, CRP, and collagen) with increased aggregate size
• however, aggregation is normal in response to thrombin and do not exhibit spontaneous aggregation upon addition of epinephrine
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• upon agonist activation, platelets exhibit moderately increased secretion compared with control cells
• in response to thrombin and CRP, ATP release is strongly increased compared to in control cells
• however, cells exhibit normal serotonin release and numbers of alpha and dense granules
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• accelerated arterial occlusive thrombus formation following ferric chloride-induced mesenteric arteriole injury
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• increased platelet size determined by increased width
• reduced filopodia extension after adhesion of immobilized VWF
• however, mice exhibit normal formation and structure of filopodia and normal spreading morphology following activation with ADP or thrombin
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• moderate
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• decreased platelet life span in vivo resulting in increased turnover
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• moderate decrease following activation with integrin alpha2bbeta3
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• at low agonist concentrations (thromboxane A2 analog U46619, CRP, and collagen) with increased aggregate size
• however, aggregation is normal in response to thrombin and do not exhibit spontaneous aggregation upon addition of epinephrine
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• upon agonist activation, platelets exhibit moderately increased secretion compared with control cells
• in response to thrombin and CRP, ATP release is strongly increased compared to in control cells
• however, cells exhibit normal serotonin release and numbers of alpha and dense granules
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice have a defect in platelet accumulation at sites of laser-induced cremaster arteriole injury
• thrombin- and convulxin-induced aggregation of platelets is decreased, however higher doses of thrombin or convulxin overcome the aggregation defect
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• ATP secretion from dense granules of platelets is about 50% of the normal platelets
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• the time to complete occlusion after FeCl3-induced injury of the carotid artery is doubled
• incorporation of platelets into a thrombus in a FeCL3-induced mesenteric artery thrombosis model is decreased
• however, platelets do not have a defect in fibrin deposition at sites of injury
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• tail bleeding times are approximately doubled
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| N |
• complete blood counts show no abnormalities and platelet counts and size are normal
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• mice have a defect in platelet accumulation at sites of laser-induced cremaster arteriole injury
• thrombin- and convulxin-induced aggregation of platelets is decreased, however higher doses of thrombin or convulxin overcome the aggregation defect
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• ATP secretion from dense granules of platelets is about 50% of the normal platelets
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• during bleed time experiments, mice die within 20 minutes if not cauterized manually
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• platelets are twice the size as in wild-type mice
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• the number of platelets is 40% of wild-type
• however, in vitro platelet half-life is normal
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• some ovoid platelets are mixed in with the normal population unlike in wild-type mice
• following activation with thrombin or U46619, platelets fail to undergo spheration unlike similarly treated wild-type platelets
• activated platelets exhibit very little shape change unlike wild-type platelets
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• platelets fail to exhibit retraction after thrombin activation unlike wild-type platelets
• at low concentrations of thrombin and U46619, platelets exhibit decreased aggregation compared to wild-type platelets
• following activation with thrombin or U46619, platelets fail to undergo spheration unlike similarly treated wild-type platelets
• serotonin release from dense granules is decreased after activation with U46619 or low concentrations of thrombin compared to similarly treated wild-type platelets
• activated platelets exhibit very little shape change unlike wild-type platelets
• activated platelets fail to form stress fibers unlike wild-type platelets
• however, platelet aggregation does occur
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• in vitro under flow conditions and in vivo, thrombus organization is impaired compared to in wild-type mice
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• platelets fail to exhibit retraction after thrombin activation unlike wild-type platelets
• at low concentrations of thrombin and U46619, platelets exhibit decreased aggregation compared to wild-type platelets
• following activation with thrombin or U46619, platelets fail to undergo spheration unlike similarly treated wild-type platelets
• serotonin release from dense granules is decreased after activation with U46619 or low concentrations of thrombin compared to similarly treated wild-type platelets
• activated platelets exhibit very little shape change unlike wild-type platelets
• activated platelets fail to form stress fibers unlike wild-type platelets
• however, platelet aggregation does occur
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• mice exhibit increased bleed time compared with wild-type mice
• during bleed time experiments, mice die within 20 minutes if not cauterized manually
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in response to low concentrations of thrombin and U46619, platelet aggregation is slight decreased compared with similarly treated wild-type cells
• in response to collagen and adenosine diphosphate, platelet aggregation is decreased compared with similarly treated wild-type cells
• in response to GPVI triggering by convulxin, platelet aggregation is abolished unlike similarly treated wild-type cells
• following FeCl3-induced injury, 90% of mice exhibit partial occlusion or fail to form thrombi unlike similarly treated wild-type mice
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• in response to low concentrations of thrombin and U46619, platelet aggregation is slight decreased compared with similarly treated wild-type cells
• in response to collagen and adenosine diphosphate, platelet aggregation is decreased compared with similarly treated wild-type cells
• in response to GPVI triggering by convulxin, platelet aggregation is abolished unlike similarly treated wild-type cells
• following FeCl3-induced injury, 90% of mice exhibit partial occlusion or fail to form thrombi unlike similarly treated wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice between 3-9 weeks of age have a 15.8% death rate compared to a 2.2% death rate among littermate controls
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• 45% fewer conditional knockout mice survive to weaning compared to littermate controls
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• megakaryocytes derived from femurs show impaired membrane-cytoskeletal association, extending membrane blebs rather than normal sheet-like lamellipodia
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• adult mice have 21% less mean red blood cell count than controls
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• adult mice have 19% less hematocrit in their blood
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• adult mice have 25% less hemoglobin in circulation
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• adult mice have 22% less platelets in their blood though the number is still in the normal range
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• platelets fail to attach to a collagen coated surface compared to control platelets that cover over 70% of the surface area
• the ability of platelets to bind fibrinogen is greatly reduced even in the presence of platelet agonists such as PAR4 peptide
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• 95% of mice over 8 weeks in age have gastrointestinal bleeding as judged by blood in fecal material
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• 95% of mice over 8 weeks in age have gastrointestinal bleeding as judged by blood in fecal material
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• 8% of 1-2 day old mice exhibit bleeding in the peritoneum
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• platelets fail to attach to a collagen coated surface compared to control platelets that cover over 70% of the surface area
• the ability of platelets to bind fibrinogen is greatly reduced even in the presence of platelet agonists such as PAR4 peptide
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• does not occur in mice after ferric chloride-induced injury of the common carotid artery
• platelets fail to form thrombi on collagen coated surfaces
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• all mice bleed for at least 10 minutes after a tail cut compared to the mean time of 4.6 minutes that control mice bleed for
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fibrogen binding is reduced compared to wild-type cells
• platelets exhibit defective agonist induced platelet integrin activation compared with wild-type mice
• however, binding in the presence of manganese is normal
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• clot retraction is impaired compared to in wild-type mice
• however, clot retraction in the presence of manganese is normal
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• fibrogen binding is reduced compared to wild-type cells
• platelets exhibit defective agonist induced platelet integrin activation compared with wild-type mice
• however, binding in the presence of manganese is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• clot retraction is impaired compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• NO-induced cGMP production is abolished in platelets compared to in control cells
• agonist-induced cGMP production is reduced in platelets compared to in control cells
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• collagen- or thrombin-induced platelet secretion and aggregation are attenuated unlike in control cells
• however, high concentrations of agonists induce normal aggregation
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• time to form FeCl3-induced carotid artery thrombosis is prolonged compared to in control mice
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| N |
• mice exhibit normal blood pressure
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| N |
• mice exhibit normal blood counts, including platelets
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• NO-induced cGMP production is abolished in platelets compared to in control cells
• agonist-induced cGMP production is reduced in platelets compared to in control cells
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• collagen- or thrombin-induced platelet secretion and aggregation are attenuated unlike in control cells
• however, high concentrations of agonists induce normal aggregation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some mice exhibit blood-filled Peyer patches unlike in wild-type mice
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• mice exhibit blood-filled mesenteric and intestinal lymphatic vessels unlike wild-type mice
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• platelets from neonates without vascular phenotypes exhibit intermediate levels of convulxin-stimulated fibrinogen binding compared with similarly treated wild-type cells
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• platelets from neonates without vascular phenotypes exhibit intermediate levels of convulxin-stimulated fibrinogen binding compared with similarly treated wild-type cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 15% of mice die postnatally due to spontaneous bleeding
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• 85% of 8-13 week old mice exhibit gastrointestinal bleeding
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• decreased hemoglobin levels
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• platelet-rich plasma (PRP) does not undergo ADP-induced platelet aggregation
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• clot retraction does not occur in platelet-rich plasma (PRP)
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• platelet-rich plasma (PRP) does not undergo ADP-induced platelet aggregation
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• 85% of 8-13 week old mice exhibit gastrointestinal bleeding
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• acute and chronic intracranial bleeding
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• acute and chronic intracranial bleeding
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Glanzmann's thrombasthenia | DOID:2219 |
OMIM:273800 |
J:224675 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• phosphatidylserine (PS) exposure and microvesiculation nearly abolished after stimulation with thrombin or collagen in vitro
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• under shear in vitro
• reduced fibrin accumulation after laser-induced injury
• reduced thrombus formation after laser-induced injury
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• phosphatidylserine (PS) exposure and microvesiculation nearly abolished after stimulation with thrombin or collagen in vitro
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• under shear in vitro
• reduced fibrin accumulation after laser-induced injury
• reduced thrombus formation after laser-induced injury
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cultured megakaryocytes derived from fetal liver E13.5 exhibit altered ploidy distribution (modal ploidy 16N compared with normal 2N) and larger size compared with control cells
• megakaryocytes are stiffer than in control cells
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• in vivo platelet production is impaired
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• in vivo platelet production is impaired
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• basic blood parameters and platelet count, ultrastructure, lifespan and mean platelet volume are normal
• megakaryocyte morphology and numbers are normal
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• impaired Ca2+ store release and store-operated Ca2+ entry (SOCE, the major route of Ca2+ influx in platelets) upon platelet activation with all tested agonists
• reduced Ca2+ concentrations in the cytoplasm of platelets upon treatment with UV light-inducible inositol 1,4,5-trisphosphate (IP3) in the absence or presence of extracellular Ca2+
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• flow cytometry revealed slightly reduced expression of glycoprotein V (GPV), GPVI, integrin beta1, and CD9 on the platelet surface
• reduced thapsigargin-evoked Ca2+ influx in the presence of extracellular Ca2+
• impaired Ca2+ store release and influx upon platelet activation with GPCR agonists (ADP, thrombin, and TxA2 analog U46619) and (hem)ITAM-dependent agonists acting on GPVI (collagen-related peptide, CRP and convulxin, CVX) or CLEC-2 (rhodocytin, RC)
• reduced Ca2+ store release and Ca2+ influx upon treatment with UV light-inducible inositol 1,4,5-trisphosphate (IP3), suggesting a functional defect of inositol trisphosphate receptors (IP3R) in platelets
• normal STIM1 (stromal interaction molecule 1) expression levels in platelet lysates
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• impaired integrin activation, degranulation, and aggregation of platelets in response to (hem)ITAM agonists under static conditions
• reduced platelet activation in response to GPVI agonists collagen-related peptide (CRP) and convulxin (CVX) or upon stimulation with the CLEC-2 agonist rhodocytin (RC)
• normal platelet activation in response to the GPCR agonists ADP, thrombin and U46619, except for a weak but significant reduction upon co-stimulation with U46619 and ADP
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• reduced platelet aggregation response to (hem)ITAM-specific stimulation, esp. at low agonist concentrations
• reduced phosphatidylserine exposure upon platelet activation in response to RC, CRP, and CRP/thrombin
• severely impaired shear-resistant platelet adhesion and aggregate formation under flow in vitro
• normal aggregation upon stimulation with the GPCR agonists thrombin, ADP, and U46619 or a combination of ADP/U46619
• no alterations in platelet ultrastructure, platelet spreading on fibrinogen or shape changes observed in aggregometry
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• impaired Ca2+ store release and store-operated Ca2+ entry (SOCE, the major route of Ca2+ influx in platelets) upon platelet activation with all tested agonists
• reduced Ca2+ concentrations in the cytoplasm of platelets upon treatment with UV light-inducible inositol 1,4,5-trisphosphate (IP3) in the absence or presence of extracellular Ca2+
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• flow cytometry revealed slightly reduced expression of glycoprotein V (GPV), GPVI, integrin beta1, and CD9 on the platelet surface
• reduced thapsigargin-evoked Ca2+ influx in the presence of extracellular Ca2+
• impaired Ca2+ store release and influx upon platelet activation with GPCR agonists (ADP, thrombin, and TxA2 analog U46619) and (hem)ITAM-dependent agonists acting on GPVI (collagen-related peptide, CRP and convulxin, CVX) or CLEC-2 (rhodocytin, RC)
• reduced Ca2+ store release and Ca2+ influx upon treatment with UV light-inducible inositol 1,4,5-trisphosphate (IP3), suggesting a functional defect of inositol trisphosphate receptors (IP3R) in platelets
• normal STIM1 (stromal interaction molecule 1) expression levels in platelet lysates
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• impaired integrin activation, degranulation, and aggregation of platelets in response to (hem)ITAM agonists under static conditions
• reduced platelet activation in response to GPVI agonists collagen-related peptide (CRP) and convulxin (CVX) or upon stimulation with the CLEC-2 agonist rhodocytin (RC)
• normal platelet activation in response to the GPCR agonists ADP, thrombin and U46619, except for a weak but significant reduction upon co-stimulation with U46619 and ADP
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• reduced platelet aggregation response to (hem)ITAM-specific stimulation, esp. at low agonist concentrations
• reduced phosphatidylserine exposure upon platelet activation in response to RC, CRP, and CRP/thrombin
• severely impaired shear-resistant platelet adhesion and aggregate formation under flow in vitro
• normal aggregation upon stimulation with the GPCR agonists thrombin, ADP, and U46619 or a combination of ADP/U46619
• no alterations in platelet ultrastructure, platelet spreading on fibrinogen or shape changes observed in aggregometry
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• following mechanical injury of the abdominal aorta, time to vessel occlusion is significantly prolonged and 3 out of 14 vessels do not occlude during the 30-min observation period
• after administration of a low dose of acetylsalicylic acid (ASA) to inhibit TxA2 synthesis, only 4 out of 14 vessels occlude
• in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke, the number of occluded vessels in the ipsilateral hemispheres is reduced relative to that in wild-type controls
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• after administration of a low dose of acetylsalicylic acid (ASA), tail bleeding times are significantly prolonged, unlike in wild-type controls
• tail bleeding times are normal in the absence of ASA treatment
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• in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke, the number of occluded vessels as well as the number of accumulated neutrophils and CD11b+ cells in the ipsilateral hemispheres are reduced relative to those in wild-type controls, indicating protection against arterial thrombosis and amelioration of thrombo-inflammatory brain infarction
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• in the tMCAO model of ischemic stroke, infarct volumes are reduced by >30% relative to those in wild-type controls
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• in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke, the number of occluded vessels as well as the number of accumulated neutrophils and CD11b+ cells in the ipsilateral hemispheres are reduced relative to those in wild-type controls, indicating protection against arterial thrombosis and amelioration of thrombo-inflammatory brain infarction
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• in the tMCAO model of ischemic stroke, infarct volumes are reduced by >30% relative to those in wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adult mice deficient in both metalloproteinases were rarely obtained (frequency: 2.5%)
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• when bone marrow is transplanted into irradiated wild-type mice, platelets treated with a calmodulin inhibitor (W7) or a mitochondrial damage reagent (CCCP) fail to shed GPVI in vitro unlike similarly treated wild-type cells
• however, in vivo shedding is normal
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• when bone marrow is transplanted into irradiated wild-type mice, platelets treated with a calmodulin inhibitor (W7) or a mitochondrial damage reagent (CCCP) fail to shed GPVI in vitro unlike similarly treated wild-type cells
• however, in vivo shedding is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• platelets exhibit impaired GPVI shedding triggered by calmodulin inhibition unlike in wild-type cells
• however, GPVI shedding induced by mitochondrial damage and antibody-induced GPVI ectodomain shedding in vivo are normal
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• platelets exhibit impaired GPVI shedding triggered by calmodulin inhibition unlike in wild-type cells
• however, GPVI shedding induced by mitochondrial damage and antibody-induced GPVI ectodomain shedding in vivo are normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• platelets exhibit normal exocytosis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in the total colony formation of megakaryocyte (CFU-MK) progenitor cells
• however, mice show a normal occlusion response following FeCl3 injury, indicating normal thrombus formation, and normal bleeding times
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in the presence of platelets, reduced migration of lymphatic endothelial cells in a transmigration assay is weaker compared to in the presence of control platelets
• platelet disruption of human lymphatic endothelial cells network formation on a matrix is disrupted to a lesser extent compared to when control platelets are used
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• at E14.5, mice exhibit blood-filled vessels unlike control mice
• at 6 to 8 weeks, mice exhibit blood in mesenteric and intestinal lymphatic vessels and intestine proper unlike in control mice
• at 8 weeks, dye injection confirms interconnection between lymphatic and blood vessels with rapid spread labeling unlike in control mice
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• in the presence of platelets, reduced migration of lymphatic endothelial cells in a transmigration assay is weaker compared to in the presence of control platelets
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• at 8 weeks, dye injection confirms interconnection between lymphatic and blood vessels with rapid spread labeling unlike in control mice
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• brain hemorrhages at E12.5
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| N |
• at P0, mice exhibit normal lungs
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• in the presence of platelets, reduced migration of lymphatic endothelial cells in a transmigration assay is weaker compared to in the presence of control platelets
• platelet disruption of human lymphatic endothelial cells network formation on a matrix is disrupted to a lesser extent compared to when control platelets are used
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• brain hemorrhages at E12.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• slight and insignificantly delayed appearance of small thrombi
• vessel occlusion is delayed or absent
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• in the presence of platelets, reduced migration of lymphatic endothelial cells in a transmigration assay is weaker compared to in the presence of control platelets
• platelet disruption of human lymphatic endothelial cells network formation on a matrix is disrupted to a lesser extent compared to when control platelets are used
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• in the presence of platelets, reduced migration of lymphatic endothelial cells in a transmigration assay is weaker compared to in the presence of control platelets
• platelet disruption of human lymphatic endothelial cells network formation on a matrix is disrupted to a lesser extent compared to when control platelets are used
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• at 8 weeks, dye injection confirms interconnection between lymphatic and blood vessels with rapid spread labeling unlike in control mice
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• brain hemorrhages at E12.5
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| N |
• at P0, mice exhibit normal lungs
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• at E14.5, mice exhibit blood-filled vessels unlike control mice
• at 6 to 8 weeks, mice exhibit blood in mesenteric and intestinal lymphatic vessels and intestine proper unlike in control mice
• at 8 weeks, dye injection confirms interconnection between lymphatic and blood vessels with rapid spread labeling unlike in control mice
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• in the presence of platelets, reduced migration of lymphatic endothelial cells in a transmigration assay is weaker compared to in the presence of control platelets
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• brain hemorrhages at E12.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• severely edematous small intestine
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• severely edematous small intestine
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• filled with blood in the mesentery and small intestine
• dilated, tortuous and rugged in appearance
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• severely edematous small intestine
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• platelets exhibit normal exocytosis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• failure of Ca2+ stimulation to increase the number of platelets that adhere to fibronectin in culture
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• failure of Ca2+ stimulation to increase the number of platelets that adhere to fibronectin in culture
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• macrothrombocytopenia
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• total numbers of clonogenic hemopoietic progenitor cells in the bone marrow and spleen are increased indicating that mice develop features of myeloproliferation
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• total number of myeloid progenitor cells in the bone marrow and spleen is increased, with a particular increase in the number of blast colony-forming cells
• blast cell colonies show increased propensity to formation of secondary colonies, particularly secondary blast cell and megakaryocyte colonies
• 2- to 4-fold increase in bone marrow LSK cells, Lin-cKit+Sca1- myeloid progenitors, pregranulocyte-macrophage progenitors, granulocyte-macrophage (GM) progenitors, and CD150+CD9(hi) and CD150+FcgammaR+ bipotential erythroid-megakaryocyte progenitor populations
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• increase in the proportion of megakaryocytes with ploidy of 16N or greater
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• mice develop megakaryocytosis in the bone marrow and spleen
• clonogenic assays of bone marrow and spleen cells show an increase in the numbers of megakaryocyte colony-forming cells
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• reduction in erythroid progenitors (preCFU-E and CFU-E)
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• mice develop thrombocytosis, with a 10-fold increase in the number of circulating platelets
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• total numbers of clonogenic hemopoietic progenitor cells in the bone marrow and spleen are increased indicating that mice develop features of myeloproliferation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• platelets treated with a glycoprotein VI (GPVI)-selective agonist, collagen-related peptide, show defects in aggregation, integrin activation, alpha-granule, dense granule, and lysosomal granule secretion, and attenuated calcium responses
• platelets show an increase in dense granule secretion and integrin activation after protease-activated receptor 4 activation, but calcium responses are unaltered
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• mice show a defect in GPVI-stimulated platelet dense granule secretion
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• platelets show an increase in dense granule secretion after protease-activated receptor 4 activation
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• platelet responses to GPVI stimulation show defects in platelet aggregation
• however, no difference in protease-activated receptor 4-activating peptide (PAR4-AP)-induced platelet aggregation is seen
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• whole blood thrombus formation over collagen is reduced
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• in a ferric chloride injury model of the carotid artery, mice show accelerated arterial thrombosis
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• mice exhibit lower bleed time levels with tail tip excision, indicating improved hemostatic function
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• small, but significant, 8.3% increase in mean platelet volume
• however, blood cell counts are unchanged
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• platelets treated with a glycoprotein VI (GPVI)-selective agonist, collagen-related peptide, show defects in aggregation, integrin activation, alpha-granule, dense granule, and lysosomal granule secretion, and attenuated calcium responses
• platelets show an increase in dense granule secretion and integrin activation after protease-activated receptor 4 activation, but calcium responses are unaltered
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• mice show a defect in GPVI-stimulated platelet dense granule secretion
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• platelets show an increase in dense granule secretion after protease-activated receptor 4 activation
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• platelet responses to GPVI stimulation show defects in platelet aggregation
• however, no difference in protease-activated receptor 4-activating peptide (PAR4-AP)-induced platelet aggregation is seen
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• mice show a defect in GPVI-stimulated platelet dense granule secretion
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• platelets show an increase in dense granule secretion after protease-activated receptor 4 activation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal platelet counts and size and fibrin deposition
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• induced by thrombin, convulxin or ADP
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• induced by thrombin, convulxin or ADP
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• bleeding in mucosal lymph nodes
• ovalbumin and CFA challenged mice develop bleeding in draining peripheral lymph nodes
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• bleeding in mucosal lymph nodes
• ovalbumin and CFA challenged mice develop bleeding in draining peripheral lymph nodes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• platelets exhibit reduced adhesion and aggregation in response to soluble collagen compared with control cells
• however, tail bleeding times are normal
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• in response to soluble collagen
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• platelets exhibit reduced adhesion and aggregation in response to soluble collagen compared with control cells
• however, tail bleeding times are normal
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• in response to soluble collagen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutant platelets have a defect in anchoring integrins to the underlying actin cytoskeleton
• mutant platelets adhered normally to collagen at low wall shear stresses and resisted detachment at wall shear stresses
• wild-type and knockout platelets adhered less well to fibrinogen
• mutant platelets adhered normally to fibrinogen at low wall shear stresses, although they detached modestly more frequently at high wall shear stresses
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• mutant platelets have a defect in anchoring integrins to the underlying actin cytoskeleton
• mutant platelets adhered normally to collagen at low wall shear stresses and resisted detachment at wall shear stresses
• wild-type and knockout platelets adhered less well to fibrinogen
• mutant platelets adhered normally to fibrinogen at low wall shear stresses, although they detached modestly more frequently at high wall shear stresses
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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