Phenotypes Associated with This Genotype

Genotype
MGI:2677136

• Allelic Composition: Itga2b^tm1Tlr/Itga2b^tm1Tlr
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ * BALB/c) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

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

growth/size/body

enlarged spleen ( J:63961 )

• 3 of 24 homozygotes display slight erythrocytopenia associated with splenomegaly

homeostasis/metabolism

abnormal hemostasis ( J:63961 )

• homozygotes display a thrombasthenic-like syndrome that prevents them from controlling blood loss

abnormal blood coagulation ( J:63961 )

abnormal platelet physiology ( J:63961 )

• 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

abnormal platelet activation ( J:63961 )

• 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

decreased platelet aggregation ( J:63961 )

• mutant platelets fail to aggregate in the presence of either ADP or collagen, unlike wild-type platelets

increased bleeding time ( J:63961 )

• adult homozygotes display a prolonged bleeding time (>15 minutes) relative to wild-type controls

integument

subcutaneous hemorrhage ( J:63961 )

• 5 of 24 adult homozygotes display subcutaneous bleeding

cardiovascular system

hemorrhage ( J:63961 )

• 12 of 24 adult homozygotes exhibit a severe bleeding diathesis at autopsy

internal hemorrhage ( J:63961 )

• 3 of 24 adult homozygotes exhibit urogenital bleeding episodes

• 3 of 24 develop obvious, but non-fatal, intra-abdominal bleeding

gastrointestinal hemorrhage ( J:63961 )

• 2 of 24 adult homozygotes exhibit gastrointestinal hemorrhage

subcutaneous hemorrhage ( J:63961 )

• 5 of 24 adult homozygotes display subcutaneous bleeding

hematopoietic system

enlarged spleen ( J:63961 )

• 3 of 24 homozygotes display slight erythrocytopenia associated with splenomegaly

decreased erythrocyte cell number ( J:63961 )

• 3 of 24 homozygotes display slight erythrocytopenia associated with splenomegaly

• however, normal numbers of white blood cells and platelets are observed

abnormal platelet alpha-granule morphology ( J:63961 )

• 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

abnormal platelet physiology ( J:63961 )

• 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

abnormal platelet activation ( J:63961 )

• 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

decreased platelet aggregation ( J:63961 )

• mutant platelets fail to aggregate in the presence of either ADP or collagen, unlike wild-type platelets

digestive/alimentary system

gastrointestinal hemorrhage ( J:63961 )

• 2 of 24 adult homozygotes exhibit gastrointestinal hemorrhage

immune system

enlarged spleen ( J:63961 )

• 3 of 24 homozygotes display slight erythrocytopenia associated with splenomegaly

reproductive system

reproductive system phenotype ( J:63961 )

N • female homozygotes are fertile with no major delivery problems, unlike women with Glanzmann thrombasthenia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
platelet-type bleeding disorder 16		DOID:0060691	OMIM:187800	J:63961