Phenotypes associated with this allele

• Allele Symbol: Pld1^tm3Mafr
• Allele Name: targeted mutation 3, Michael Frohman
• Allele ID: MGI:5575654
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pld1^tm3Mafr/Pld1^tm3Mafr	B6.129-Pld1^tm3Mafr	MGI:5829678
hm2	Pld1^tm3Mafr/Pld1^tm3Mafr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5575658
cx3	Pld1^tm3Mafr/Pld1^tm3Mafr Pld2^tm1(KOMP)Vlcg/Pld2^tm1(KOMP)Vlcg	involves: C57BL/6 * C57BL/6NTac	MGI:5829681

Genotype
MGI:5829678

hm1

• Allelic Composition: Pld1^tm3Mafr/Pld1^tm3Mafr
• Genetic Background: B6.129-Pld1^tm3Mafr

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

hematopoietic system

abnormal platelet activation ( J:216114 )

• integrin activation is slightly reduced upon stimulation with low and intermediate concentrations of thrombin or protease-activated receptor 4 (PAR4)-activating peptide

• however, no defect in integrin activation is noted upon submaximal platelet activation with collagen-related peptide (CRP)

homeostasis/metabolism

abnormal platelet activation ( J:216114 )

• integrin activation is slightly reduced upon stimulation with low and intermediate concentrations of thrombin or protease-activated receptor 4 (PAR4)-activating peptide

• however, no defect in integrin activation is noted upon submaximal platelet activation with collagen-related peptide (CRP)

Genotype
MGI:5575658

hm2

• Allelic Composition: Pld1^tm3Mafr/Pld1^tm3Mafr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:211547 )

• following induction of lethal pulmonary thromboembolism with collagen and epinephrine

homeostasis/metabolism

decreased platelet aggregation ( J:211547 )

• unstable under high shear flow conditions

• however, aggregation under low and intermediate shear conditions is normal

decreased susceptibility to injury ( J:211547 )

• following induction of lethal pulmonary thromboembolism with collagen and epinephrine

• following topical application of ferric chloride to the carotid artery, only 2 of 7 mice exhibit transient occlusion compared with all but one wild-type mice that exhibit full occlusion

• following mechanical induction of thrombosis in the aorta, fewer mice exhibit irreversible occlusion compared with wild-type mice

decreased susceptibility to ischemic brain injury ( J:211547 )

• following focal cerebral ischemia, mice exhibit decreased infarct size, no intracranial hemorrhage and improved motor function and coordination compared with wild-type mice

• however, mice reconstituted with wild-type bone marrow exhibit normal infarcts

decreased cerebral infarct size ( J:211547 )

• following focal cerebral ischemia

hematopoietic system

increased mean platelet volume ( J:211547 )

• slightly

decreased platelet aggregation ( J:211547 )

• unstable under high shear flow conditions

• however, aggregation under low and intermediate shear conditions is normal

nervous system

decreased susceptibility to ischemic brain injury ( J:211547 )

• following focal cerebral ischemia, mice exhibit decreased infarct size, no intracranial hemorrhage and improved motor function and coordination compared with wild-type mice

• however, mice reconstituted with wild-type bone marrow exhibit normal infarcts

decreased cerebral infarct size ( J:211547 )

• following focal cerebral ischemia

Genotype
MGI:5829681

cx3

• Allelic Composition: Pld1^tm3Mafr/Pld1^tm3Mafr; Pld2^{tm1(KOMP)Vlcg}/Pld2^{tm1(KOMP)Vlcg}
• Genetic Background: involves: C57BL/6 * C57BL/6NTac
• Cell Lines: 11541B-D1

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:216114 )

N • mice exhibit normal tail bleeding times, indicating normal hemostasis

abnormal platelet activation ( J:216114 )

• platelets show reduced alpha-granule release upon stimulation of protease-activated receptor 4 (PAR4) with either thrombin or PAR4-activating peptide, as determined by the levels of surface exposed P-selectin

• secretion of the alpha-granular proteins von Willebrand factor (VWF) and platelet factor 4 (PF4) is decreased relative to that in wild-type platelets

• integrin activation is markedly reduced upon stimulation with low and intermediate concentrations of thrombin or PAR4-activating peptide

• no differences in reactivity are observed in aggregometry

• the amount and localization of alpha granules and agonist-induced ATP release (a measure of dense granule secretion) are normal

decreased susceptibility to induced thrombosis ( J:216114 )

• in the FeCl3-induced mesenteric arteriole injury model, 12 of 34 double mutant vessels fail to show full occlusion within the 40 min observation period, whereas only 4 of 38 wild-type vessels remain open

• when full occlusion occurs, time to stable occlusion is significantly longer than that in wild-type controls, indicating protection from FeCl3-induced arteriolar thrombosis

abnormal enzyme/coenzyme activity ( J:216114 )

• agonist-induced phospholipase D (PLD) activity is completely abolished in platelets

decreased susceptibility to ischemic brain injury ( J:216114 )

• in the transient middle cerebral artery occlusion (tMCAO) model, brain infarct volume is reduced to ~60% of that in wild-type controls and the neurologic Bederson score is significantly improved 24 h after tMCAO, indicating protection from ischemic stroke

decreased cerebral infarct size ( J:216114 )

• at 24 h after tMCAO, brain infarct volume is reduced to ~60% of that in wild-type controls

hematopoietic system

abnormal platelet activation ( J:216114 )

• platelets show reduced alpha-granule release upon stimulation of protease-activated receptor 4 (PAR4) with either thrombin or PAR4-activating peptide, as determined by the levels of surface exposed P-selectin

• secretion of the alpha-granular proteins von Willebrand factor (VWF) and platelet factor 4 (PF4) is decreased relative to that in wild-type platelets

• integrin activation is markedly reduced upon stimulation with low and intermediate concentrations of thrombin or PAR4-activating peptide

• no differences in reactivity are observed in aggregometry

• the amount and localization of alpha granules and agonist-induced ATP release (a measure of dense granule secretion) are normal

nervous system

decreased susceptibility to ischemic brain injury ( J:216114 )

• in the transient middle cerebral artery occlusion (tMCAO) model, brain infarct volume is reduced to ~60% of that in wild-type controls and the neurologic Bederson score is significantly improved 24 h after tMCAO, indicating protection from ischemic stroke

decreased cerebral infarct size ( J:216114 )

• at 24 h after tMCAO, brain infarct volume is reduced to ~60% of that in wild-type controls