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Phenotypes Associated with This Genotype
Genotype
MGI:2177829
Allelic
Composition
Itgb3tm1Hyn/Itgb3tm1Hyn
Genetic
Background
involves: 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Itgb3tm1Hyn mutation (6 available); any Itgb3 mutation (43 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Survival of Itgb3tm1Hyn/Itgb3tm1Hyn mice is compromised due to placental defects and hemorrhage

growth/size/body
• heart weight to body weight ratio is increased
• in 12-week-old spontaneous cardiac hypertrophy occurs in the absence of provocative stimulation
• commonly associated with gastrointestinal bleeding

mortality/aging
• some homozygous animals suffered acute blood loss and crisis which lead to premature death
• significant loss of homozygous pups up to three weeks of age due to hemorrhage

cardiovascular system
• hypoxia-induced retinal neovascularization is significantly elevated as measure by numbers of vascular glomeruli at P17
• significantly elevated numbers of vessels per square millimeter of tumors, from injected cells, when compared with wild-type controls
• blood-vessel infiltration of matrigel implants impregnated with VEGF is significantly elevated
• in the presence of VEGF, the total number of vessel sprouts in aortic rings embedded in Matrigel is significantly higher compared to wild-type
• however, no increase in vessel density is seen on scruff skin
• heart weight to body weight ratio is increased
• in 12-week-old spontaneous cardiac hypertrophy occurs in the absence of provocative stimulation
• left ventricle weight to body weight ratio is increased by 4 weeks of age
• some homozygous embryos and newborn pups displayed hemorrhage in the skin, in petechiae and in purpura, and appeared anemic
• in some homozygous newborn pups which die before weaning and in many of the surviving homozygous adult mice
• a significantly impaired contractile response to infusion of the inotropic agent Dobutamine
• diastolic relaxation is impaired (dP/dt min and tau (Glantz) are significantly increased)
• 12-week-old mice have reduced systolic function compared to wild-type littermates
• left ventricular peak systolic pressure is significantly decreased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type
• left ventricular peak systolic pressure is decreased in 12-week-old mice
• left ventricular end-diastolic pressure is significantly increased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type
• the maximal change in pressure per unit time is significantly decreased 7 days after pressure overload by TAC surgery compared to wild-type
• minimal change in pressure per unit time is significantly increased 7 days after pressure overload by TAC surgery compared to wild-type
• heart rate is significantly decreased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type
• impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls
• cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery

hematopoietic system
• commonly associated with gastrointestinal bleeding
• found in animals with splenomegaly
• secondary to the excessive bleeding
• in 8-12-week-old mice
• in 8-12-week-old mice
• in 8-12-week-old mice
• the monocyte count is dramatically increased in peripheral blood
• in 8-12-week-old mice
• peritoneal macrophages express significantly more Tnf and Il1b
• peritoneal macrophages migrate less efficiently
• 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
• platelet isolated from homozygous mice did not aggregate after ADP-induced activation in vitro
• platelet isolated from homozygous mice shows reduced clot retraction and greatly reduced fibrinogen uptake in vitro

reproductive system
• 9.5% of the embryos carried by homozygous mothers were found dead in utero at E14 and E17
• compromised survival of embryos in homozygous mother as a result of placental defects and intrauterine hemorrhage
• litter sizes of homozygous female were reduced significantly compared to wild-type

embryo
• within affected placentae of homozygous pregnant females, trophoblastic cells sometimes invaded the labyrinthine part of the placenta
• thickened cell layers in the labyrinth layer in approximately 25% of placentae of homozygous pregnant females which were associated with dead embryos
• within affected placentae, the space between endothelial layers was reduced with evidence of increased necrosis

digestive/alimentary system
• in some homozygous newborn pups which die before weaning and in many of the surviving homozygous adult mice

immune system
• commonly associated with gastrointestinal bleeding
• the monocyte count is dramatically increased in peripheral blood
• peritoneal macrophages express significantly more Tnf and Il1b
• peritoneal macrophages migrate less efficiently
• cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery
• ulcerative dermatitis in some homozygous animals undergoing crisis

homeostasis/metabolism
• impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls
• cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery
• 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
• platelet isolated from homozygous mice did not aggregate after ADP-induced activation in vitro
• platelet isolated from homozygous mice shows reduced clot retraction and greatly reduced fibrinogen uptake in vitro
• impaired hemostasis as evidenced by failure to arrest bleeding within 10 minutes following tail resection

renal/urinary system
• enlarged glomeruli and dilated and necrotic proximal tubules containing proteinaceous deposits are found secondary to the excessive bleeding

liver/biliary system
• centrilobular necrosis of the liver are found secondary to the excessive bleeding

vision/eye
N
• the patterns of neovascularization in P7 retinas isolated from wild-type or homozygous mutant mice showed no obvious differences
• hypoxia-induced retinal neovascularization is significantly elevated as measure by numbers of vascular glomeruli at P17

neoplasm
• significantly elevated numbers of vessels per square millimeter of tumors, from injected cells, when compared with wild-type controls
• tumor size is enhanced significantly when injected with murine melanoma (B16F0) or lung carcinoma (CMT19T) cells

cellular
• endothelial cells showed background levels of adhesion and no migration on vitronectin
• centrilobular necrosis of the liver are found secondary to the excessive bleeding
• enlarged glomeruli and dilated and necrotic proximal tubules containing proteinaceous deposits are found secondary to the excessive bleeding
• endothelial cells showed background levels of adhesion and no migration on vitronectin
• peritoneal macrophages migrate less efficiently

muscle
• a significantly impaired contractile response to infusion of the inotropic agent Dobutamine
• diastolic relaxation is impaired (dP/dt min and tau (Glantz) are significantly increased)
• cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery

integument
• ulcerative dermatitis in some homozygous animals undergoing crisis
• petechiae are observed around the mouth, indicating bleeding under the epidermis
• purpura are observed on the forelimb, indicating bleeding within the dermis

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
platelet-type bleeding disorder 16 DOID:0060691 OMIM:187800
J:52262


Contributing Projects:
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
03/19/2024
MGI 6.23
The Jackson Laboratory