cardiovascular system phenotype

• abnormal cardiac muscle relaxation
  • diastolic relaxation is impaired (dP/dt min and tau (Glantz) are significantly increased)
  (MGI Ref ID J:119666)

• abnormal induced retinal neovascularization
  • hypoxia-induced retinal neovascularization is significantly elevated as measure by numbers of vascular glomeruli at P17
  (MGI Ref ID J:73752)

• abnormal tumor vascularization
  • significantly elevated numbers of vessels per square millimeter of tumors, from injected cells, when compared with wild-type controls
  (MGI Ref ID J:73752)

• cardiac hypertrophy
  • in 12-week-old spontaneous cardiac hypertrophy occurs in the absence of provocative stimulation
  (MGI Ref ID J:119666)

• decreased cardiac muscle contractility
  • a significantly impaired contractile response to infusion of the inotropic agent Dobutamine
  (MGI Ref ID J:119666)

• decreased heart rate
  • heart rate is significantly decreased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type
  (MGI Ref ID J:119666)

• decreased left ventricle systolic pressure
  • 12-week-old mice have reduced systolic function compared to wild-type littermates
  (MGI Ref ID J:119666)
  • left ventricular peak systolic pressure is decreased in 12-week-old mice
  (MGI Ref ID J:119666)
  • left ventricular peak systolic pressure is significantly decreased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type
  (MGI Ref ID J:119666)

• gastrointestinal hemorrhage
  • in some homozygous newborn pups which die before weaning and in many of the surviving homozygous adult mice
  (MGI Ref ID J:52262)

• heart left ventricle hypertrophy
  (MGI Ref ID J:119666)

• hemorrhage
  • some homozygous embryos and newborn pups displayed hemorrhage in the skin, in petechiae and in purpura, and appeared anemic
  (MGI Ref ID J:52262)

• increased angiogenesis
  • blood-vessel infiltration of matrigel implants impregnated with VEGF is significantly elevated
  (MGI Ref ID J:73752)
  • however, no increase in vessel density is seen on scruff skin
  (MGI Ref ID J:73752)
  • in the presence of VEGF, the total number of vessel sprouts in aortic rings embedded in Matrigel is significantly higher compared to wild-type
  (MGI Ref ID J:73752)

• increased heart weight
  • heart weight to body weight ratio is increased
  (MGI Ref ID J:119666)

• increased left ventricle diastolic pressure
  • left ventricular end-diastolic pressure is significantly increased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type
  (MGI Ref ID J:119666)
  • minimal change in pressure per unit time is significantly increased 7 days after pressure overload by TAC surgery compared to wild-type
  (MGI Ref ID J:119666)
  • the maximal change in pressure per unit time is significantly decreased 7 days after pressure overload by TAC surgery compared to wild-type
  (MGI Ref ID J:119666)

• increased left ventricle weight
  • left ventricle weight to body weight ratio is increased by 4 weeks of age
  (MGI Ref ID J:119666)

• increased response of heart to induced stress
  • cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery
  (MGI Ref ID J:119666)
  • impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls
  (MGI Ref ID J:119666)

• petechiae
  • petechiae are observed around the mouth, indicating bleeding under the epidermis
  (MGI Ref ID J:52262)

• purpura
  • purpura are observed on the forelimb, indicating bleeding within the dermis
  (MGI Ref ID J:52262)

• uterine hemorrhage
  (MGI Ref ID J:52262)

cellular phenotype

• abnormal cell adhesion
  • endothelial cells showed background levels of adhesion and no migration on vitronectin
  (MGI Ref ID J:73752)

• abnormal cell migration
  • endothelial cells showed background levels of adhesion and no migration on vitronectin
  (MGI Ref ID J:73752)

• hepatic necrosis
  • centrilobular necrosis of the liver are found secondary to the excessive bleeding
  (MGI Ref ID J:52262)

• impaired macrophage chemotaxis
  • peritoneal macrophages migrate less efficiently
  (MGI Ref ID J:119666)

• renal necrosis
  • enlarged glomeruli and dilated and necrotic proximal tubules containing proteinaceous deposits are found secondary to the excessive bleeding
  (MGI Ref ID J:52262)

digestive/alimentary phenotype

• gastrointestinal hemorrhage
  • in some homozygous newborn pups which die before weaning and in many of the surviving homozygous adult mice
  (MGI Ref ID J:52262)

embryo phenotype

• abnormal placenta labyrinth morphology
  • thickened cell layers in the labyrinth layer in approximately 25% of placentae of homozygous pregnant females which were associated with dead embryos
  (MGI Ref ID J:52262)
  • within affected placentae, the space between endothelial layers was reduced with evidence of increased necrosis
  (MGI Ref ID J:52262)

• abnormal trophoblast giant cell morphology
  • within affected placentae of homozygous pregnant females, trophoblastic cells sometimes invaded the labyrinthine part of the placenta
  (MGI Ref ID J:52262)

• pale placenta
  (MGI Ref ID J:52262)

hematopoietic system phenotype

• abnormal macrophage physiology
  • peritoneal macrophages express significantly more Tnf and Il1b
  (MGI Ref ID J:119666)

• abnormal platelet activation
  • platelet isolated from homozygous mice did not aggregate after ADP-induced activation in vitro
  (MGI Ref ID J:52262)
  • platelet isolated from homozygous mice shows reduced clot retraction and greatly reduced fibrinogen uptake in vitro
  (MGI Ref ID J:52262)
  • reduced formation of thrombi in Shwartzman-like reaction, an experimental model of hemorrhagic vasculitis induced by subcutaneous injection of LPS followed 24 h later by an injection of TNF-alpha in the same place
  (MGI Ref ID J:52262)

• anemia
  • secondary to the excessive bleeding
  (MGI Ref ID J:52262)

• decreased erythrocyte cell number
  • in 8-12-week-old mice
  (MGI Ref ID J:52262)

• decreased hematocrit
  • in 8-12-week-old mice
  (MGI Ref ID J:52262)

• decreased hemoglobin content
  • in 8-12-week-old mice
  (MGI Ref ID J:52262)

• enlarged spleen
  • commonly associated with gastrointestinal bleeding
  (MGI Ref ID J:52262)

• extramedullary hematopoiesis
  • found in animals with splenomegaly
  (MGI Ref ID J:52262)

• impaired macrophage chemotaxis
  • peritoneal macrophages migrate less efficiently
  (MGI Ref ID J:119666)

• increased monocyte cell number
  • the monocyte count is dramatically increased in peripheral blood
  (MGI Ref ID J:119666)

• reticulocytosis
  • in 8-12-week-old mice
  (MGI Ref ID J:52262)

homeostasis/metabolism phenotype

• abnormal platelet activation
  • platelet isolated from homozygous mice did not aggregate after ADP-induced activation in vitro
  (MGI Ref ID J:52262)
  • platelet isolated from homozygous mice shows reduced clot retraction and greatly reduced fibrinogen uptake in vitro
  (MGI Ref ID J:52262)
  • reduced formation of thrombi in Shwartzman-like reaction, an experimental model of hemorrhagic vasculitis induced by subcutaneous injection of LPS followed 24 h later by an injection of TNF-alpha in the same place
  (MGI Ref ID J:52262)

• increased bleeding time
  • impaired hemostasis as evidenced by failure to arrest bleeding within 10 minutes following tail resection
  (MGI Ref ID J:52262)

• increased response of heart to induced stress
  • cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery
  (MGI Ref ID J:119666)
  • impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls
  (MGI Ref ID J:119666)

immune system phenotype

• abnormal macrophage physiology
  • peritoneal macrophages express significantly more Tnf and Il1b
  (MGI Ref ID J:119666)

• dermatitis
  • ulcerative dermatitis in some homozygous animals undergoing crisis
  (MGI Ref ID J:52262)

• enlarged spleen
  • commonly associated with gastrointestinal bleeding
  (MGI Ref ID J:52262)

• impaired macrophage chemotaxis
  • peritoneal macrophages migrate less efficiently
  (MGI Ref ID J:119666)

• increased monocyte cell number
  • the monocyte count is dramatically increased in peripheral blood
  (MGI Ref ID J:119666)

• myositis
  • cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery
  (MGI Ref ID J:119666)

integument phenotype

• dermatitis
  • ulcerative dermatitis in some homozygous animals undergoing crisis
  (MGI Ref ID J:52262)

• petechiae
  • petechiae are observed around the mouth, indicating bleeding under the epidermis
  (MGI Ref ID J:52262)

• purpura
  • purpura are observed on the forelimb, indicating bleeding within the dermis
  (MGI Ref ID J:52262)

liver/biliary system phenotype

• hepatic necrosis
  • centrilobular necrosis of the liver are found secondary to the excessive bleeding
  (MGI Ref ID J:52262)

mammalian phenotype

• vision/eye phenotype
  • Normal - the patterns of neovascularization in P7 retinas isolated from wild-type or homozygous mutant mice showed no obvious differences
  (MGI Ref ID J:52262)

mortality/aging

• postnatal lethality, incomplete penetrance
  • significant loss of homozygous pups up to three weeks of age due to hemorrhage
  (MGI Ref ID J:52262)

• premature death
  • some homozygous animals suffered acute blood loss and crisis which lead to premature death
  (MGI Ref ID J:52262)

muscle phenotype

• abnormal cardiac muscle relaxation
  • diastolic relaxation is impaired (dP/dt min and tau (Glantz) are significantly increased)
  (MGI Ref ID J:119666)

• decreased cardiac muscle contractility
  • a significantly impaired contractile response to infusion of the inotropic agent Dobutamine
  (MGI Ref ID J:119666)

• heart left ventricle hypertrophy
  (MGI Ref ID J:119666)

• myositis
  • cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery
  (MGI Ref ID J:119666)

neoplasm

• abnormal tumor vascularization
  • significantly elevated numbers of vessels per square millimeter of tumors, from injected cells, when compared with wild-type controls
  (MGI Ref ID J:73752)

• increased tumor growth/size
  • tumor size is enhanced significantly when injected with murine melanoma (B16F0) or lung carcinoma (CMT19T) cells
  (MGI Ref ID J:73752)

renal/urinary system phenotype

• renal necrosis
  • enlarged glomeruli and dilated and necrotic proximal tubules containing proteinaceous deposits are found secondary to the excessive bleeding
  (MGI Ref ID J:52262)

reproductive system phenotype

• abnormal miscarriage rate
  • 9.5% of the embryos carried by homozygous mothers were found dead in utero at E14 and E17
  (MGI Ref ID J:52262)

• abnormal uterine environment
  • compromised survival of embryos in homozygous mother as a result of placental defects and intrauterine hemorrhage
  (MGI Ref ID J:52262)

• reduced female fertility
  • litter sizes of homozygous female were reduced significantly compared to wild-type
  (MGI Ref ID J:52262)

• uterine hemorrhage
  (MGI Ref ID J:52262)

vision/eye phenotype

• abnormal induced retinal neovascularization
  • hypoxia-induced retinal neovascularization is significantly elevated as measure by numbers of vascular glomeruli at P17
  (MGI Ref ID J:73752)

cardiovascular system phenotype

• cardiac hypertrophy
  • the hypertrophy phenotype is intermediate between homozygous null and wild-type mice
  (MGI Ref ID J:119666)

• decreased heart rate
  • heart rate is significantly decreased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type
  (MGI Ref ID J:119666)

• heart left ventricle hypertrophy
  • spontaneous
  (MGI Ref ID J:119666)

• increased heart weight
  • heart weight to body weight ratio is increased
  (MGI Ref ID J:119666)

• increased left ventricle weight
  • left ventricle weight to body weight ratio is increased
  (MGI Ref ID J:119666)

• increased response of heart to induced stress
  • heart rate is significantly decreased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type
  (MGI Ref ID J:119666)
  • impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls
  (MGI Ref ID J:119666)

muscle phenotype

• heart left ventricle hypertrophy
  • spontaneous
  (MGI Ref ID J:119666)

homeostasis/metabolism phenotype

• increased response of heart to induced stress
  • heart rate is significantly decreased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type
  (MGI Ref ID J:119666)
  • impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls
  (MGI Ref ID J:119666)

cellular phenotype

• maternal effect
  • gotes
  (MGI Ref ID J:131241)
  • heterozygous pups from non-immunized females mated with wild-type males exhibit normal platelets counts, indicating that maternal antibodies of the pregnant females and not pup genotype is responsible for the reduced platelets and hemorrhaging in heterozygotes
  (MGI Ref ID J:131241)
  • loimmune thrombocytopenia
  (MGI Ref ID J:131241)
  • pups and fetuses from homozygous females immunized two or four times with wild-type platelets, respectively, and mated with wild-type males exhibit hemorrhaging, reduced platelets and increased mortality, a phenotype similar to human fetal and neonatal alloimmune thrombocytopenia
  (MGI Ref ID J:131241)

mortality/aging

• pregnancy-related premature death
  • one of three homozygous females immunized four times with wild-type platelets and mated with a wild-type male, died during delivery after a 3-week pregnancy
  (MGI Ref ID J:131241)

reproductive system phenotype

• abnormal miscarriage rate
  • homozygous females immunized with wild-type platelets and mated with wild-type males, exhibit miscarriages due to internal organ bleeding of fetuses; females immunized 4 times show more miscarriages than females immunized 2 times with wild-type platelets
  (MGI Ref ID J:131241)

hematopoietic system phenotype

• increased IgG level
  • however, homozygous preimmunized females do not show any detectable anti-Itgb3 IgG after the first and second deliveries after mating with wild-type males; low levels of anti-Itgb3 antibodies are seen in the third and subsequent deliveries
  (MGI Ref ID J:131241)
  • titer of maternal IgG against Itgb3 in homozygous females increases with the number of times females are immunized with wild-type platelets
  (MGI Ref ID J:131241)

immune system phenotype

• increased IgG level
  • however, homozygous preimmunized females do not show any detectable anti-Itgb3 IgG after the first and second deliveries after mating with wild-type males; low levels of anti-Itgb3 antibodies are seen in the third and subsequent deliveries
  (MGI Ref ID J:131241)
  • titer of maternal IgG against Itgb3 in homozygous females increases with the number of times females are immunized with wild-type platelets
  (MGI Ref ID J:131241)

mammalian phenotype

• immune system phenotype
  • Normal - both T-helper 1 and T-helper 2 immune responses to platelet Itgb3 antigen exist in mutants
  (MGI Ref ID J:131241)

cardiovascular system phenotype

• abnormal physiological neovascularization
  • increase in vascularization in wounds after 7 days of healing
  (MGI Ref ID J:96049)

immune system phenotype

• abnormal osteoclast morphology
  • actin rings fail to form and actin is diffusely distributed, in a punctate pattern
  (MGI Ref ID J:60672)
  • the ruffled membrane is thick with blunted projections
  (MGI Ref ID J:60672)

• abnormal osteoclast physiology
  • bone marrow macrophages differentiate into osteoclasts that fail to spread
  (MGI Ref ID J:60672)

• decreased macrophage cell number
  • number of macrophage in wounds is significantly lower than in wild-type wounds
  (MGI Ref ID J:96049)

• increased osteoclast cell number
  • about a 3 fold increase per mm trabecular bone surface
  (MGI Ref ID J:60672)

integument phenotype

• decreased keratinocyte proliferation
  • in the hyperproliferative epidermal region 3 days after wounding
  (MGI Ref ID J:96049)

cellular phenotype

• decreased keratinocyte proliferation
  • in the hyperproliferative epidermal region 3 days after wounding
  (MGI Ref ID J:96049)

skeleton phenotype

• abnormal osteoclast morphology
  • actin rings fail to form and actin is diffusely distributed, in a punctate pattern
  (MGI Ref ID J:60672)
  • the ruffled membrane is thick with blunted projections
  (MGI Ref ID J:60672)

• abnormal osteoclast physiology
  • bone marrow macrophages differentiate into osteoclasts that fail to spread
  (MGI Ref ID J:60672)

• increased compact bone thickness
  • increased bone mass
  (MGI Ref ID J:60672)

• increased osteoclast cell number
  • about a 3 fold increase per mm trabecular bone surface
  (MGI Ref ID J:60672)

• increased trabecular bone thickness
  • decreased ability of bone marrow macrophage derived osteoclasts to excavate whale dentin and produce well defined resorption lacunae
  (MGI Ref ID J:60672)

• osteosclerosis
  • increased bone mass
  (MGI Ref ID J:60672)

hematopoietic system phenotype

• abnormal osteoclast morphology
  • actin rings fail to form and actin is diffusely distributed, in a punctate pattern
  (MGI Ref ID J:60672)
  • the ruffled membrane is thick with blunted projections
  (MGI Ref ID J:60672)

• abnormal osteoclast physiology
  • bone marrow macrophages differentiate into osteoclasts that fail to spread
  (MGI Ref ID J:60672)

• abnormal platelet physiology
  • platelets release twofold more TGF
  (MGI Ref ID J:96049)

• decreased macrophage cell number
  • number of macrophage in wounds is significantly lower than in wild-type wounds
  (MGI Ref ID J:96049)

• increased osteoclast cell number
  • about a 3 fold increase per mm trabecular bone surface
  (MGI Ref ID J:60672)

homeostasis/metabolism phenotype

• abnormal platelet physiology
  • platelets release twofold more TGF
  (MGI Ref ID J:96049)

• decreased circulating calcium level
  (MGI Ref ID J:60672)

• enhanced wound healing
  • dermal fibroblast recruitment in wounded tissue is significantly elevated with enhanced fibronectin and vitronectin deposition in granulation tissue
  (MGI Ref ID J:96049)
  • re-epithelialization is accelerated significantly
  (MGI Ref ID J:96049)

• increased transforming growth factor level
  • platelets release twofold more TGF
  (MGI Ref ID J:96049)