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Allele Symbol Allele Name Allele ID |
Pik3c2atm1Bvan targeted mutation 1, Bart Vanhaesebroeck MGI:5779550 |
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| Summary |
2 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• megakaryocytes show defects in membrane and alpha-granule morphology, as shown by TEM analysis of bone marrow
• the demarcation membrane system is less developed and delineated
• fewer alpha-granules, heterogeneous in shape and bigger than wild-type, are observed
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• at 8-14 weeks of age, hematocrit is slightly increased relative to wild-type controls
• however, other blood parameters such as RBC, WBC, hemoglobin concentration, mean globular volume, and immune cell populations (B cells, T cells, granulocytes) are normal
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• platelets display an altered open canalicular system and are heterogeneous in size, as shown by increased platelet distribution width confirmed by tubulin ring diameter measurement
• 31% of resting platelets show an invaginated and tortuous (rough) plasma membrane shape relative to 4.2% in wild-type platelets
• however, platelet count, mean platelet volume, and the number, size and content of platelet dense granules are normal
• platelet life span and platelet count recovery after immune-induced thrombocytopenia are normal
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• an increased number of barbell shaped-proplatelets (platelets with 2 cell bodies), which are normally very rare, is observed by TEM analysis
• % of barbell proplatelets is markeldy increased in freshly obtained washed platelets, in washed platelets cultured in suspension for 24 hours, and in washed platelets after perfusion over a vWF-coated microcapillary
• enrichment of barbell proplatelets suggests a defect in the scission required to produce mature platelets, possibly related to the abnormal membrane structure seen in megakaryocytes and platelets
• bone marrow transplantation experiments confirmed that enrichment in barbell-shaped proplatelets is due to a hematopoietic cell defect
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• platelets show an abnormal alpha-granule distribution with a 46.0% decrease in number and a 60.5% increase in size relative to wild-type platelets
• however, global platelet alpha-granule content such as vWF and fibrinogen is normal
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• 46.0% decrease in number
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• although platelets are able to exhibit shape change after stimulation by collagen-related peptide (CRP) or thrombin, they show a severe defect in filopodia extension relative to wild-type platelets
• atomic force microscopy revealed a significantly higher Young's modulus indicating that platelets are more rigid than wild-type platelets
• platelets have normal major lipid composition but show aberrant recruitment and/or stabilization of several membrane skeleton proteins that are required for normal platelet membrane shape and dynamics
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• resting platelets show a reduction in the basal, agonist-insensitive, pool of PI3P
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• in vitro platelet aggregation in response to low doses of collagen or CRP is reduced, but increasing the doses of agonists restores a normal response
• platelet aggregation in response to thrombin, thromboxane A2 analog (U46619), or adenosine diphosphate is normal
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| N |
• heterozygotes show normal bleeding time, suggesting normal hemostasis
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• resting platelets show a reduction in the basal, agonist-insensitive, pool of PI3P
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• in vitro platelet aggregation in response to low doses of collagen or CRP is reduced, but increasing the doses of agonists restores a normal response
• platelet aggregation in response to thrombin, thromboxane A2 analog (U46619), or adenosine diphosphate is normal
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• after ferric chloride injury of the carotid artery, heterozygotes show a significant delay in artery occlusion relative to wild-type controls
• ex vivo thrombus formation assay performed on a collagen matrix at arterial shear rate showed a significant decrease in the area covered by thrombi and in thrombus volume relative to wild-type controls
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• an increased number of barbell shaped-proplatelets (platelets with 2 cell bodies), which are normally very rare, is observed by TEM analysis
• % of barbell proplatelets is markeldy increased in freshly obtained washed platelets, in washed platelets cultured in suspension for 24 hours, and in washed platelets after perfusion over a vWF-coated microcapillary
• enrichment of barbell proplatelets suggests a defect in the scission required to produce mature platelets, possibly related to the abnormal membrane structure seen in megakaryocytes and platelets
• bone marrow transplantation experiments confirmed that enrichment in barbell-shaped proplatelets is due to a hematopoietic cell defect
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• platelets and megakaryocytes show major defects in plasma membrane morphology
• platelets show mislocalization of several membrane skeleton proteins known to control the interactions between the plasma membrane and cytoskeleton
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| N |
• heterozygotes show no signs of spontaneous bleeding
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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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last database update 05/07/2024 MGI 6.23 |
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