Mouse Genome Informatics
hm
    Nbeal2tm1Lex/Nbeal2tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
hematopoietic system
• mature bone marrow megakaryocytes lack alpha-granules, show increased number of vacuoles and mitochondria, and show presence of leukocytes inside the cytoplasm, indicating emperipolesis
• fetal liver cell- and bone marrow-derived megakaryocytes either lack Von Willebrand factor (VWF) or show accumulation of the protein in distinct cytoplasmic areas between the nucleus and the plasma membrane and show irregular deposition of actin
• platelets show an increased number of vacuoles, which appear empty, with no electron-dense material inside
• platelets contain only 11% of the wild-type level of Von Willebrand factor (VWF)
• moderate macrothrombocytopenia, with platelet size increased by about 14% and count reduced by about 40%
• however, basic blood parameters and immune cell populations are unaltered
• absence of alpha-granules in platelets, however delta-granules are not affected and in rare cases alpha-granule remnants are seen
• 2-fold increase in the number of splenic megakaryocytes and a minor increase in the number of bone marrow megakaryocytes in both young and 6-month old mutants
• mild splenomegaly is seen in 6-week old mutants but does not develop further
• platelets show reduced degranulation-dependent P-selectin exposure compared to wild-type platelets in response to tested agonists
• platelets show reduced aggregation upon stimulation with collagen, collagen-related peptide, or PAR-4 peptide
• platelets exhibit defective adhesion and aggregate formation under flow over collagen, indicating impaired thrombi formation; the surface area covered by platelets and the total thrombus volume are reduced by about 85% and 88%, respectively
• the procoagulant index is reduced by 2 orders of magnitude in platelets

homeostasis/metabolism
• following ferric chloride-induced mesenteric arteriole injury, mutants show an unchanged onset of thrombus formation, however the rapid progression to full occlusive thrombus formation is impaired due to the formation of unstable platelet aggregates which disintegrate rapidly
• following abdominal aorta injury, 7 of 8 mutants do not show occlusive thrombus formation during a 30 minute observation
• platelets show reduced degranulation-dependent P-selectin exposure compared to wild-type platelets in response to tested agonists
• platelets show reduced aggregation upon stimulation with collagen, collagen-related peptide, or PAR-4 peptide
• platelets exhibit defective adhesion and aggregate formation under flow over collagen, indicating impaired thrombi formation; the surface area covered by platelets and the total thrombus volume are reduced by about 85% and 88%, respectively
• the procoagulant index is reduced by 2 orders of magnitude in platelets
• mutants exhibit increased tail bleeding times, with no mutants stopping bleeding within the time frame that wild-type mice stop
• mutants show impaired occlusive thrombus formation following ferric chloride-induced mesenteric arteriole injury or abdominal aorta injury
• mutants exhibit impaired dermal healing following skin wounding, showing a reduced area of underlying granulation tissue compared to control wounds, less developed collagenous tissue, and fewer myofibroblasts in the wound area
• mutants are protected from thrombo-inflammatory brain infarction following focal cerebral ischemia, showing reduced infract size

nervous system
• mutants are protected from thrombo-inflammatory brain infarction following focal cerebral ischemia, showing reduced infract size

immune system
• mild splenomegaly is seen in 6-week old mutants but does not develop further

cellular
• myofibroblast differentiation is impaired during wound repair

Mouse Models of Human Disease
OMIM IDRef(s)
Gray Platelet Syndrome; GPS 139090 J:201413