Mouse Genome Informatics
hm1
    Itga2btm1Tlr/Itga2btm1Tlr
either: (involves: 129S1/Sv * 129X1/SvJ * BALB/c) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• homozygotes display a thrombasthenic-like syndrome that prevents them from controlling blood loss
• unlike platelet-rich plasma (PRP) from wild-type controls which complete the retraction of opaque thrombin-induced clots within a 2-hr period, mutant PRP fails to undergo clot retraction for 15 hours
• mutant platelets have a severely reduced capacity to bind fibrinogen relative to wild-type platelets
• specific and displaceable fibrinogen binding is only 6% +/- 2% of normal
• mutant platelets fail to aggregate in the presence of either ADP or collagen, unlike wild-type platelets
• adult homozygotes display a prolonged bleeding time (>15 minutes) relative to wild-type controls

cardiovascular system
• 12 of 24 adult homozygotes exhibit a severe bleeding diathesis at autopsy
• 2 of 24 adult homozygotes exhibit gastrointestinal hemorrhage
• 5 of 24 adult homozygotes display subcutaneous bleeding
• 2 of 24 show gastrointestinal hemorrhage
• 3 of 24 exhibit urogenital bleeding episodes
• 3 of 24 develop obvious, but non-fatal, intra-abdominal bleeding

hematopoietic system
• 3 of 24 homozygotes display slight erythrocytopenia associated with splenomegaly
• however, normal numbers of white blood cells and platelets are observed
• mutant platelet alpha-granules do not contain fibrinogen, unlike wild-type organelles
• however, immunogold labeling and ultrastructural analysis of megakaryocytes indicates normal morphology with normal alpha-granule organization relative to wild-type controls
• 3 of 24 homozygotes display slight erythrocytopenia associated with splenomegaly
• unlike platelet-rich plasma (PRP) from wild-type controls which complete the retraction of opaque thrombin-induced clots within a 2-hr period, mutant PRP fails to undergo clot retraction for 15 hours
• mutant platelets have a severely reduced capacity to bind fibrinogen relative to wild-type platelets
• specific and displaceable fibrinogen binding is only 6% +/- 2% of normal
• mutant platelets fail to aggregate in the presence of either ADP or collagen, unlike wild-type platelets

digestive/alimentary system
• 2 of 24 adult homozygotes exhibit gastrointestinal hemorrhage

immune system
• 3 of 24 homozygotes display slight erythrocytopenia associated with splenomegaly

reproductive system
N
• female homozygotes are fertile with no major delivery problems, unlike women with Glanzmann thrombasthenia (J:63961)

Mouse Models of Human Disease
OMIM IDRef(s)
Bleeding Disorder, Platelet-Type, 16; BDPLT16 187800 J:63961


Mouse Genome Informatics
ht2
    Itga2btm1Tlr/Itga2b+
either: (involves: 129S1/Sv * 129X1/SvJ * BALB/c) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• unlike platelet-rich plasma (PRP) from wild-type controls which complete the retraction of opaque thrombin-induced clots within a 2-hr period, heterozygous PRP shows both a delayed and incomplete clot retraction during this period
• heterozygous platelets display a specific fibrinogen binding capacity of 57% relative to 100% in wild-type platelets
• although heterozygous platelets exhibit substantial aggregation in response to ADP or collagen, the collagen response is significantly delayed relative to that in wild-type controls

hematopoietic system
• unlike platelet-rich plasma (PRP) from wild-type controls which complete the retraction of opaque thrombin-induced clots within a 2-hr period, heterozygous PRP shows both a delayed and incomplete clot retraction during this period
• heterozygous platelets display a specific fibrinogen binding capacity of 57% relative to 100% in wild-type platelets
• although heterozygous platelets exhibit substantial aggregation in response to ADP or collagen, the collagen response is significantly delayed relative to that in wild-type controls


Mouse Genome Informatics
cx3
    Itga2btm1Tlr/Itga2btm1Tlr
Vwftm1.1Diac/Vwftm1.1Diac

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• form normal thrombi in response to arteriolar injury (J:181672)