Phenotypes associated with this allele

• Allele Symbol: Bin2^tm1.1Beni
• Allele Name: targeted mutation 1.1, Bernhard Nieswandt
• Allele ID: MGI:6508532
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Bin2^tm1.1Beni/Bin2^tm1.1Beni Tg(Pf4-icre)Q3Rsko/0	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac	MGI:6510837

Genotype
MGI:6510837

cn1

• Allelic Composition: Bin2^tm1.1Beni/Bin2^tm1.1Beni; Tg(Pf4-icre)Q3Rsko/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NTac

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

hematopoietic system

hematopoietic system phenotype ( J:302510 )

N • basic blood parameters and platelet count, ultrastructure, lifespan and mean platelet volume are normal

N • megakaryocyte morphology and numbers are normal

abnormal platelet calcium level ( J:302510 )

• 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⁺

abnormal platelet physiology ( J:302510 )

• 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

abnormal platelet activation ( J:302510 )

• 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

decreased platelet aggregation ( J:302510 )

• 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

homeostasis/metabolism

abnormal platelet calcium level ( J:302510 )

• 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⁺

abnormal platelet physiology ( J:302510 )

• 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

abnormal platelet activation ( J:302510 )

• 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

decreased platelet aggregation ( J:302510 )

• 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

decreased susceptibility to induced thrombosis ( J:302510 )

• 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

increased bleeding time ( J:302510 )

• 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

decreased susceptibility to ischemic brain injury ( J:302510 )

• 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

decreased cerebral infarct size ( J:302510 )

• in the tMCAO model of ischemic stroke, infarct volumes are reduced by >30% relative to those in wild-type controls

nervous system

decreased susceptibility to ischemic brain injury ( J:302510 )

• 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

decreased cerebral infarct size ( J:302510 )

• in the tMCAO model of ischemic stroke, infarct volumes are reduced by >30% relative to those in wild-type controls