Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   01-MAR-06 Species laboratory mouse Generation F?+F10N1F16 (27-NOV-11) Generation Definitions   Donating Investigator Dr. Richard Hynes,   Massachusetts Institute of Technology

Description
Mice that are homozygous for this targeted allele are viable and fertile. No gene product (protein) is detected on the surface of platelets. Significant (50%) embryonic lethality attributed to fetal hemorrhaging and placental defects is observed. Until three weeks of age, additional pup loss may occur due to hemorrhaging in the skin and gastrointestinal tract. Gastrointestinal tract bleeding is commonly observed in adults and is frequently associated with an enlarged spleen. Erythrocyte number, hemoglobin, hematocrits and thrombus formation are all reduced while bleeding time is prolonged. Varying degrees of liver and kidney necrosis are also observed. Although increased numbers of osteoclasts are observed (3.5 fold over that seen in heterozygotes) they appear to be dysfunctional, having a reduced ability to resorb whale dentin in vitro. Mice are osteosclerotic and hypocalcemic. Enhanced tumor angiogenesis and vascular endothelial growth factor-induced blood vessel growth are observed. This mutant mouse strain represents a model that may be useful in studies related to Glanzmann thrombasthenia.

Development
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt exons 1 and 2 of the targeted gene. The construct was transfected into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice and made homozygous.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Itgb3^tm1Hyn allele

008700	129S-Itgb3tm1Hyn/J
008698	B6.129S2-Itgb3tm1Hyn/J
008819	B6.129S2-Itgb3tm1Hyn/JSemJ
008699	C.129S2-Itgb3tm1Hyn/J

View Strains carrying   Itgb3^tm1Hyn     (4 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Bleeding Disorder, Platelet-Type, 16; BDPLT16

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Glanzmann Thrombasthenia; GT   (ITGB3) Integrin, Beta-3; ITGB3   (ITGB3) Myocardial Infarction, Susceptibility to   (ITGB3)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Itgb3^tm1Hyn/Itgb3⁺

        involves: 129S2/SvPas * C57BL/6

• cardiovascular system phenotype
• cardiac hypertrophy
  • the hypertrophy phenotype is intermediate between homozygous null and wild-type mice   (MGI Ref ID J:119666)
• • heart left ventricle hypertrophy
    • spontaneous   (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)
• 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
  • impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls   (MGI Ref ID J:119666)
  • 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)
• homeostasis/metabolism phenotype
• increased response of heart to induced stress
  • impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls   (MGI Ref ID J:119666)
  • 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)

Itgb3^tm1Hyn/Itgb3^tm1Hyn

        involves: 129S2/SvPas * C57BL/6

• mortality/aging
• partial postnatal lethality
  • 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)
• 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)
• • heart left ventricle hypertrophy   (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 significantly decreased 7 days after pressure overload by transverse aortic constriction surgery (TAC) compared to wild-type   (MGI Ref ID J:119666)
  • left ventricular peak systolic pressure is decreased in 12-week-old mice   (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)
• • 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)
  • 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)
• increased angiogenesis
  • blood-vessel infiltration of matrigel implants impregnated with VEGF is significantly elevated   (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)
  • however, no increase in vessel density is seen on scruff skin   (MGI Ref ID J:73752)
• 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 by 4 weeks of age   (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)
  • 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)
  • 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)
• increased response of heart to induced stress
  • impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls   (MGI Ref ID J:119666)
  • cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery   (MGI Ref ID J:119666)
• hematopoietic system phenotype
• abnormal platelet activation
  • 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)
  • 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)
• 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)
• 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)
• reproductive system phenotype
• abnormal spontaneous abortion 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)
• embryogenesis 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 cells
  • 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)
• 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)
• immune system phenotype
• abnormal macrophage physiology
  • peritoneal macrophages express significantly more Tnf and Il1b   (MGI Ref ID J:119666)
• • impaired macrophage chemotaxis
    • peritoneal macrophages migrate less efficiently   (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)
• 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)
• homeostasis/metabolism phenotype
• abnormal platelet activation
  • 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)
  • 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)
• 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
  • impairment of systolic and diastolic function after transverse aortic constriction is more severe than in wild-type controls   (MGI Ref ID J:119666)
  • cardiac tissue exhibits marked round cell infiltration 7 days after transverse aortic constriction surgery   (MGI Ref ID J:119666)
• 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)
• liver/biliary system phenotype
• hepatic necrosis
  • centrilobular necrosis of the liver are found secondary to the excessive bleeding   (MGI Ref ID J:52262)
• vision/eye phenotype
• *normal* vision/eye phenotype
  • the patterns of neovascularization in P7 retinas isolated from wild-type or homozygous mutant mice showed no obvious differences   (MGI Ref ID J:52262)
• • 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)
• tumorigenesis
• 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)
• 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)
• • impaired macrophage chemotaxis
    • peritoneal macrophages migrate less efficiently   (MGI Ref ID J:119666)
• 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)
• 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)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Itgb3^tm1Hyn/Itgb3^tm1Hyn

        involves: 129S2/SvPas

• skeleton phenotype
• abnormal osteoclast morphology
  • the ruffled membrane is thick with blunted projections   (MGI Ref ID J:60672)
  • actin rings fail to form and actin is diffusely distributed, in a punctate pattern   (MGI Ref ID J:60672)
• • increased osteoclast cell number
    • about a 3 fold increase per mm trabecular bone surface   (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 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
  • the ruffled membrane is thick with blunted projections   (MGI Ref ID J:60672)
  • actin rings fail to form and actin is diffusely distributed, in a punctate pattern   (MGI Ref ID J:60672)
• • increased osteoclast cell number
    • about a 3 fold increase per mm trabecular bone surface   (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)
• immune system phenotype
• abnormal osteoclast morphology
  • the ruffled membrane is thick with blunted projections   (MGI Ref ID J:60672)
  • actin rings fail to form and actin is diffusely distributed, in a punctate pattern   (MGI Ref ID J:60672)
• • increased osteoclast cell number
    • about a 3 fold increase per mm trabecular bone surface   (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)
• 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
  • re-epithelialization is accelerated significantly   (MGI Ref ID J:96049)
  • dermal fibroblast recruitment in wounded tissue is significantly elevated with enhanced fibronectin and vitronectin deposition in granulation tissue   (MGI Ref ID J:96049)
• increased transforming growth factor level
  • platelets release twofold more TGF   (MGI Ref ID J:96049)
• cardiovascular system phenotype
• abnormal physiological neovascularization
  • increase in vascularization in wounds after 7 days of healing   (MGI Ref ID J:96049)
• 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)

Itgb3^tm1Hyn/Itgb3^tm1Hyn

        involves: 129S2/SvPas * BALB/c

• 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)
• other phenotype
• maternal effect
  • 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)
  • 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)
• reproductive system phenotype
• abnormal spontaneous abortion 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)
• immune system phenotype
• *normal* immune system phenotype
  • both T-helper 1 and T-helper 2 immune responses to platelet Itgb3 antigen exist in mutants   (MGI Ref ID J:131241)
• • increased IgG level
    • 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)
    • 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)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Developmental Biology Research
Embryonic Lethality (Homozygous)
      incomplete

Internal/Organ Research
Skeleton
      Bone

Itgb3^tm1Hyn related

Cardiovascular Research
Vascular Defects

Hematological Research
Clotting Defects
Platelet Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Itgb3tm1Hyn
Allele Name		targeted mutation 1, Richard Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		Beta3; beta3 KO; beta3-;
Mutation Made By		Dr. Richard Hynes,   Massachusetts Institute of Technology
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Itgb3, integrin beta 3
Chromosome		11
Gene Common Name(s)		BDPLT16; BDPLT2; CD61; GP3A; GPIIIa; GT; platelet glycoprotein IIIa (GP3A);
Molecular Note		A PGK-neomycin resistance cassette replaced 1.4 kb of sequence including exons I and II. FACS, immunoprecipitation, and immunofluorescence analyses did not detect protein expression in platelets and MEFs from homozygous mutant animals. [MGI Ref ID J:52262]

Genotyping

Genotyping Information

Genotyping Protocols

Itgb3^tm1Hynalternate1,

SEPARATED MELT

Itgb3^tm1Hynalternate1, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Hodivala-Dilke KM; McHugh KP; Tsakiris DA; Rayburn H; Crowley D; Ullman-Cullere M; Ross FP; Coller BS; Teitelbaum S; Hynes RO. 1999. Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest 103(2):229-38. [PubMed: 9916135]  [MGI Ref ID J:52262]

Additional References

McHugh KP; Hodivala-Dilke K; Zheng MH; Namba N; Lam J; Novack D; Feng X; Ross FP; Hynes RO; Teitelbaum SL. 2000. Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts. J Clin Invest 105(4):433-40. [PubMed: 10683372]  [MGI Ref ID J:60672]

Reynolds LE; Wyder L; Lively JC; Taverna D; Robinson SD; Huang X; Sheppard D; Hynes RO; Hodivala-Dilke KM. 2002. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 8(1):27-34. [PubMed: 11786903]  [MGI Ref ID J:73752]

Itgb3^tm1Hyn related

Andre P; Denis CV; Ware J; Saffaripour S; Hynes RO; Ruggeri ZM; Wagner DD. 2000. Platelets adhere to and translocate on von willebrand factor presented by endothelium in stimulated veins Blood 96(10):3322-8. [PubMed: 11071623]  [MGI Ref ID J:65812]

Andre P; Prasad KS; Denis CV; He M; Papalia JM; Hynes RO; Phillips DR; Wagner DD. 2002. CD40L stabilizes arterial thrombi by a beta3 integrin--dependent mechanism. Nat Med 8(3):247-52. [PubMed: 11875495]  [MGI Ref ID J:75152]

Aslam R; Hu Y; Gebremeskel S; Segel GB; Speck ER; Guo L; Kim M; Ni H; Freedman J; Semple JW. 2012. Thymic retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia. Blood 120(10):2127-32. [PubMed: 22760780]  [MGI Ref ID J:189178]

Bakewell SJ; Nestor P; Prasad S; Tomasson MH; Dowland N; Mehrotra M; Scarborough R; Kanter J; Abe K; Phillips D; Weilbaecher KN. 2003. Platelet and osteoclast beta3 integrins are critical for bone metastasis. Proc Natl Acad Sci U S A 100(24):14205-10. [PubMed: 14612570]  [MGI Ref ID J:86702]

Balasubramanian S; Quinones L; Kasiganesan H; Zhang Y; Pleasant DL; Sundararaj KP; Zile MR; Bradshaw AD; Kuppuswamy D. 2012. beta3 integrin in cardiac fibroblast is critical for extracellular matrix accumulation during pressure overload hypertrophy in mouse. PLoS One 7(9):e45076. [PubMed: 22984613]  [MGI Ref ID J:191757]

Bergmeier W; Goerge T; Wang HW; Crittenden JR; Baldwin AC; Cifuni SM; Housman DE; Graybiel AM; Wagner DD. 2007. Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III. J Clin Invest 117(6):1699-707. [PubMed: 17492052]  [MGI Ref ID J:122618]

Bergmeier W; Piffath CL; Goerge T; Cifuni SM; Ruggeri ZM; Ware J; Wagner DD. 2006. The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci U S A 103(45):16900-5. [PubMed: 17075060]  [MGI Ref ID J:117137]

Boosani CS; Mannam AP; Cosgrove D; Silva R; Hodivala-Dilke KM; Keshamouni VG; Sudhakar A. 2007. Regulation of COX-2 mediated signaling by alpha3 type IV noncollagenous domain in tumor angiogenesis. Blood 110(4):1168-77. [PubMed: 17426256]  [MGI Ref ID J:145399]

Carneiro AM; Cook EH; Murphy DL; Blakely RD. 2008. Interactions between integrin alphaIIbbeta3 and the serotonin transporter regulate serotonin transport and platelet aggregation in mice and humans. J Clin Invest 118(4):1544-52. [PubMed: 18317590]  [MGI Ref ID J:135834]

Chauhan AK; Motto DG; Lamb CB; Bergmeier W; Dockal M; Plaimauer B; Scheiflinger F; Ginsburg D; Wagner DD. 2006. Systemic antithrombotic effects of ADAMTS13. J Exp Med 203(3):767-76. [PubMed: 16533881]  [MGI Ref ID J:123759]

Chen P; Li C; Lang S; Zhu G; Reheman A; Spring CM; Freedman J; Ni H. 2010. Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy. Blood 116(18):3660-8. [PubMed: 20647570]  [MGI Ref ID J:166478]

Cho J; Kennedy DR; Lin L; Huang M; Merrill-Skoloff G; Furie BC; Furie B. 2012. Protein disulfide isomerase capture during thrombus formation in vivo depends on the presence of beta3 integrins. Blood 120(3):647-55. [PubMed: 22653978]  [MGI Ref ID J:189109]

Chow L; Aslam R; Speck ER; Kim M; Cridland N; Webster ML; Chen P; Sahib K; Ni H; Lazarus AH; Garvey MB; Freedman J; Semple JW. 2010. A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy. Blood 115(6):1247-53. [PubMed: 20007808]  [MGI Ref ID J:157730]

Chun TH; Sabeh F; Ota I; Murphy H; McDonagh KT; Holmbeck K; Birkedal-Hansen H; Allen ED; Weiss SJ. 2004. MT1-MMP-dependent neovessel formation within the confines of the three-dimensional extracellular matrix. J Cell Biol 167(4):757-67. [PubMed: 15545316]  [MGI Ref ID J:94371]

D'Amico G; Robinson SD; Germain M; Reynolds LE; Thomas GJ; Elia G; Saunders G; Fruttiger M; Tybulewicz V; Mavria G; Hodivala-Dilke KM. 2010. Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent. PLoS One 5(3):e9766. [PubMed: 20339539]  [MGI Ref ID J:158882]

Destaing O; Planus E; Bouvard D; Oddou C; Badowski C; Bossy V; Raducanu A; Fourcade B; Albiges-Rizo C; Block MR. 2010. beta1A integrin is a master regulator of invadosome organization and function. Mol Biol Cell 21(23):4108-19. [PubMed: 20926684]  [MGI Ref ID J:182932]

Di Paolo NC; Miao EA; Iwakura Y; Murali-Krishna K; Aderem A; Flavell RA; Papayannopoulou T; Shayakhmetov DM. 2009. Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo. Immunity 31(1):110-21. [PubMed: 19576795]  [MGI Ref ID J:151628]

Fang J; Hodivala-Dilke K; Johnson BD; Du LM; Hynes RO; White GC 2nd; Wilcox DA. 2005. Therapeutic expression of the platelet-specific integrin, alphaIIbbeta3, in a murine model for Glanzmann thrombasthenia. Blood 106(8):2671-9. [PubMed: 15972454]  [MGI Ref ID J:119539]

Feng W; Madajka M; Kerr BA; Mahabeleshwar GH; Whiteheart SW; Byzova TV. 2011. A novel role for platelet secretion in angiogenesis: mediating bone marrow-derived cell mobilization and homing. Blood 117(14):3893-902. [PubMed: 21224474]  [MGI Ref ID J:172614]

Feng X; Novack DV; Faccio R; Ory DS; Aya K; Boyer MI; McHugh KP; Ross FP; Teitelbaum SL. 2001. A Glanzmann's mutation in beta 3 integrin specifically impairs osteoclast function. J Clin Invest 107(9):1137-44. [PubMed: 11342577]  [MGI Ref ID J:120522]

Frederix K; Chauhan AK; Kisucka J; Zhao BQ; Hoff EI; Spronk HM; Ten Cate H; Wagner DD. 2007. Platelet adhesion receptors do not modulate infarct volume after a photochemically induced stroke in mice. Brain Res 1185:239-45. [PubMed: 17996853]  [MGI Ref ID J:130124]

Fuchs TA; Bhandari AA; Wagner DD. 2011. Histones induce rapid and profound thrombocytopenia in mice. Blood 118(13):3708-14. [PubMed: 21700775]  [MGI Ref ID J:176912]

Goerge T; Ho-Tin-Noe B; Carbo C; Benarafa C; Remold-O'Donnell E; Zhao BQ; Cifuni SM; Wagner DD. 2008. Inflammation induces hemorrhage in thrombocytopenia. Blood 111(10):4958-64. [PubMed: 18256319]  [MGI Ref ID J:135316]

Guo M; Daines D; Tang J; Shen Q; Perrin RM; Takada Y; Yuan SY; Wu MH. 2009. Fibrinogen-gamma C-terminal fragments induce endothelial barrier dysfunction and microvascular leak via integrin-mediated and RhoA-dependent mechanism. Arterioscler Thromb Vasc Biol 29(3):394-400. [PubMed: 19122172]  [MGI Ref ID J:159784]

Hamano Y; Zeisberg M; Sugimoto H; Lively JC; Maeshima Y; Yang C; Hynes RO; Werb Z; Sudhakar A; Kalluri R. 2003. Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell 3(6):589-601. [PubMed: 12842087]  [MGI Ref ID J:120382]

Ho-Tin-Noe B; Carbo C; Demers M; Cifuni SM; Goerge T; Wagner DD. 2009. Innate immune cells induce hemorrhage in tumors during thrombocytopenia. Am J Pathol 175(4):1699-708. [PubMed: 19729481]  [MGI Ref ID J:153057]

Iannacone M; Sitia G; Isogawa M; Whitmire JK; Marchese P; Chisari FV; Ruggeri ZM; Guidotti LG. 2008. Platelets prevent IFN-alpha/beta-induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic choriomeningitis virus. Proc Natl Acad Sci U S A 105(2):629-34. [PubMed: 18184798]  [MGI Ref ID J:131089]

Joly S; Samardzija M; Wenzel A; Thiersch M; Grimm C. 2009. Nonessential role of beta3 and beta5 integrin subunits for efficient clearance of cellular debris after light-induced photoreceptor degeneration. Invest Ophthalmol Vis Sci 50(3):1423-32. [PubMed: 18997092]  [MGI Ref ID J:146677]

Jones DT; Lechertier T; Reynolds LE; Mitter R; Robinson SD; Kirn-Safran CB; Hodivala-Dilke KM. 2013. Endogenous ribosomal protein L29 (RPL29): a newly identified regulator of angiogenesis in mice. Dis Model Mech 6(1):115-24. [PubMed: 23118343]  [MGI Ref ID J:193723]

Kanamori M; Kawaguchi T; Berger MS; Pieper RO. 2006. Intracranial microenvironment reveals independent opposing functions of host alphaVbeta3 expression on glioma growth and angiogenesis. J Biol Chem 281(48):37256-64. [PubMed: 17028191]  [MGI Ref ID J:117661]

Lacy-Hulbert A; Ueno T; Ito T; Jurewicz M; Izawa A; Smith RN; Chase CM; Tanaka K; Fiorina P; Russell PS; Auchincloss H Jr; Sayegh MH; Hynes RO; Abdi R. 2007. Beta 3 integrins regulate lymphocyte migration and cytokine responses in heart transplant rejection. Am J Transplant 7(5):1080-90. [PubMed: 17359504]  [MGI Ref ID J:134650]

Lakshmikanthan S; Sobczak M; Chun C; Henschel A; Dargatz J; Ramchandran R; Chrzanowska-Wodnicka M. 2011. Rap1 promotes VEGFR2 activation and angiogenesis by a mechanism involving integrin alphavbeta. Blood 118(7):2015-26. [PubMed: 21636859]  [MGI Ref ID J:176941]

Li C; Piran S; Chen P; Lang S; Zarpellon A; Jin JW; Zhu G; Reheman A; van der Wal DE; Simpson EK; Ni R; Gross PL; Ware J; Ruggeri ZM; Freedman J; Ni H. 2011. The maternal immune response to fetal platelet GPIbalpha causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies. J Clin Invest 121(11):4537-47. [PubMed: 22019589]  [MGI Ref ID J:178708]

Li Z; Nardi MA; Li YS; Zhang W; Pan R; Dang S; Yee H; Quartermain D; Jonas S; Karpatkin S. 2009. C-terminal ADAMTS-18 fragment induces oxidative platelet fragmentation, dissolves platelet aggregates, and protects against carotid artery occlusion and cerebral stroke. Blood 113(24):6051-60. [PubMed: 19218546]  [MGI Ref ID J:149378]

Liu H; Niu A; Chen SE; Li YP. 2011. {beta}3-Integrin mediates satellite cell differentiation in regenerating mouse muscle. FASEB J 25(6):1914-21. [PubMed: 21350117]  [MGI Ref ID J:172759]

McHugh KP; Hodivala-Dilke K; Zheng MH; Namba N; Lam J; Novack D; Feng X; Ross FP; Hynes RO; Teitelbaum SL. 2000. Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts. J Clin Invest 105(4):433-40. [PubMed: 10683372]  [MGI Ref ID J:60672]

Murugaiyan G; Mittal A; Weiner HL. 2008. Increased osteopontin expression in dendritic cells amplifies IL-17 production by CD4+ T cells in experimental autoimmune encephalomyelitis and in multiple sclerosis. J Immunol 181(11):7480-8. [PubMed: 19017937]  [MGI Ref ID J:142205]

Ni H; Chen P; Spring CM; Sayeh E; Semple JW; Lazarus AH; Hynes RO; Freedman J. 2006. A novel murine model of fetal and neonatal alloimmune thrombocytopenia: response to intravenous IgG therapy. Blood 107(7):2976-83. [PubMed: 16317099]  [MGI Ref ID J:131241]

Ni H; Papalia JM; Degen JL; Wagner DD. 2003. Control of thrombus embolization and fibronectin internalization by integrin alpha IIb beta 3 engagement of the fibrinogen gamma chain. Blood 102(10):3609-14. [PubMed: 12855554]  [MGI Ref ID J:86449]

Nishimoto T; Satoh T; Simpson EK; Ni H; Kuwana M. 2013. Predominant autoantibody response to GPIb/IX in a regulatory T-cell-deficient mouse model for immune thrombocytopenia. J Thromb Haemost 11(2):369-72. [PubMed: 23176290]  [MGI Ref ID J:195458]

Penvose A; Westerman KA. 2012. Sca-1 is involved in the adhesion of myosphere cells to alphaVbeta3 Biol Open 1:839-847.  [MGI Ref ID J:187361]

Petrich BG; Fogelstrand P; Partridge AW; Yousefi N; Ablooglu AJ; Shattil SJ; Ginsberg MH. 2007. The antithrombotic potential of selective blockade of talin-dependent integrin alpha IIb beta 3 (platelet GPIIb-IIIa) activation. J Clin Invest 117(8):2250-9. [PubMed: 17627302]  [MGI Ref ID J:123968]

Reheman A; Yang H; Zhu G; Jin W; He F; Spring CM; Bai X; Gross PL; Freedman J; Ni H. 2009. Plasma fibronectin depletion enhances platelet aggregation and thrombus formation in mice lacking fibrinogen and von Willebrand factor. Blood 113(8):1809-17. [PubMed: 19036705]  [MGI Ref ID J:145550]

Ren J; Avery J; Zhao H; Schneider JG; Ross FP; Muslin AJ. 2007. Beta3 integrin deficiency promotes cardiac hypertrophy and inflammation. J Mol Cell Cardiol 42(2):367-77. [PubMed: 17184791]  [MGI Ref ID J:119666]

Reynolds AR; Reynolds LE; Nagel TE; Lively JC; Robinson SD; Hicklin DJ; Bodary SC; Hodivala-Dilke KM. 2004. Elevated Flk1 (vascular endothelial growth factor receptor 2) signaling mediates enhanced angiogenesis in beta3-integrin-deficient mice. Cancer Res 64(23):8643-50. [PubMed: 15574772]  [MGI Ref ID J:94450]

Reynolds LE; Conti FJ; Lucas M; Grose R; Robinson S; Stone M; Saunders G; Dickson C; Hynes RO; Lacy-Hulbert A; Hodivala-Dilke K. 2005. Accelerated re-epithelialization in beta(3)-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling. Nat Med 11(2):167-174. [PubMed: 15654327]  [MGI Ref ID J:96049]

Reynolds LE; Wyder L; Lively JC; Taverna D; Robinson SD; Huang X; Sheppard D; Hynes RO; Hodivala-Dilke KM. 2002. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 8(1):27-34. [PubMed: 11786903]  [MGI Ref ID J:73752]

Schmidt S; Nakchbandi I; Ruppert R; Kawelke N; Hess MW; Pfaller K; Jurdic P; Fassler R; Moser M. 2011. Kindlin-3-mediated signaling from multiple integrin classes is required for osteoclast-mediated bone resorption. J Cell Biol 192(5):883-97. [PubMed: 21357746]  [MGI Ref ID J:170685]

Schneider JG; Zhu Y; Coleman T; Semenkovich CF. 2007. Macrophage beta3 integrin suppresses hyperlipidemia-induced inflammation by modulating TNFalpha expression. Arterioscler Thromb Vasc Biol 27(12):2699-706. [PubMed: 17951320]  [MGI Ref ID J:141525]

Schulz O; Pennington DJ; Hodivala-Dilke K; Febbraio M; Reis e Sousa C. 2002. CD36 or alphavbeta3 and alphavbeta5 integrins are not essential for MHC class I cross-presentation of cell-associated antigen by CD8 alpha+ murine dendritic cells. J Immunol 168(12):6057-65. [PubMed: 12055214]  [MGI Ref ID J:123797]

Smyth SS; Reis ED; Vaananen H; Zhang W; Coller BS. 2001. Variable protection of beta 3-integrin--deficient mice from thrombosis initiated by different mechanisms. Blood 98(4):1055-62. [PubMed: 11493451]  [MGI Ref ID J:71133]

Su X; Floyd DH; Hughes A; Xiang J; Schneider JG; Uluckan O; Heller E; Deng H; Zou W; Craft CS; Wu K; Hirbe AC; Grabowska D; Eagleton MC; Townsley S; Collins L; Piwnica-Worms D; Steinberg TH; Novack DV; Conley PB; Hurchla MA; Rogers M; Weilbaecher KN. 2012. The ADP receptor P2RY12 regulates osteoclast function and pathologic bone remodeling. J Clin Invest 122(10):3579-92. [PubMed: 22996695]  [MGI Ref ID J:192464]

Svendsen OS; Liden A; Nedrebo T; Rubin K; Reed RK. 2008. Integrin {alpha}v{beta}3 acts downstream of insulin in normalization of interstitial fluid pressure in sepsis and in cell-mediated collagen gel contraction. Am J Physiol Heart Circ Physiol 295(2):H555-60. [PubMed: 18552165]  [MGI Ref ID J:138224]

Taverna D; Crowley D; Connolly M; Bronson RT; Hynes RO. 2005. A direct test of potential roles for beta3 and beta5 integrins in growth and metastasis of murine mammary carcinomas. Cancer Res 65(22):10324-9. [PubMed: 16288021]  [MGI Ref ID J:103405]

Taverna D; Moher H; Crowley D; Borsig L; Varki A; Hynes RO. 2004. Increased primary tumor growth in mice null for beta3- or beta3/beta5-integrins or selectins. Proc Natl Acad Sci U S A 101(3):763-8. [PubMed: 14718670]  [MGI Ref ID J:88109]

Umemoto T; Yamato M; Ishihara J; Shiratsuchi Y; Utsumi M; Morita Y; Tsukui H; Terasawa M; Shibata T; Nishida K; Kobayashi Y; Petrich BG; Nakauchi H; Eto K; Okano T. 2012. Integrin-alphavbeta3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells. Blood 119(1):83-94. [PubMed: 22096247]  [MGI Ref ID J:181799]

Wei C; Moller CC; Altintas MM; Li J; Schwarz K; Zacchigna S; Xie L; Henger A; Schmid H; Rastaldi MP; Cowan P; Kretzler M; Parrilla R; Bendayan M; Gupta V; Nikolic B; Kalluri R; Carmeliet P; Mundel P; Reiser J. 2008. Modification of kidney barrier function by the urokinase receptor. Nat Med 14(1):55-63. [PubMed: 18084301]  [MGI Ref ID J:130835]

Weng S; Zemany L; Standley KN; Novack DV; La Regina M; Bernal-Mizrachi C; Coleman T; Semenkovich CF. 2003. Beta3 integrin deficiency promotes atherosclerosis and pulmonary inflammation in high-fat-fed, hyperlipidemic mice. Proc Natl Acad Sci U S A 100(11):6730-5. [PubMed: 12746502]  [MGI Ref ID J:83615]

Xie L; Duncan MB; Pahler J; Sugimoto H; Martino M; Lively J; Mundel T; Soubasakos M; Rubin K; Takeda T; Inoue M; Lawler J; Hynes RO; Hanahan D; Kalluri R. 2011. Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner. Proc Natl Acad Sci U S A 108(24):9939-44. [PubMed: 21622854]  [MGI Ref ID J:173322]

Yang H; Lang S; Zhai Z; Li L; Kahr WH; Chen P; Brkic J; Spring CM; Flick MJ; Degen JL; Freedman J; Ni H. 2009. Fibrinogen is required for maintenance of platelet intracellular and cell-surface P-selectin expression. Blood 114(2):425-36. [PubMed: 19332769]  [MGI Ref ID J:150774]

Yang H; Reheman A; Chen P; Zhu G; Hynes RO; Freedman J; Wagner DD; Ni H. 2006. Fibrinogen and von Willebrand factor-independent platelet aggregation in vitro and in vivo. J Thromb Haemost 4(10):2230-7. [PubMed: 16824188]  [MGI Ref ID J:129287]

Yang Q; McHugh KP; Patntirapong S; Gu X; Wunderlich L; Hauschka PV. 2008. VEGF enhancement of osteoclast survival and bone resorption involves VEGF receptor-2 signaling and beta3-integrin. Matrix Biol 27(7):589-99. [PubMed: 18640270]  [MGI Ref ID J:144608]

Zhang L; Dong Y; Dong Y; Cheng J; Du J. 2012. Role of integrin-beta3 protein in macrophage polarization and regeneration of injured muscle. J Biol Chem 287(9):6177-86. [PubMed: 22210777]  [MGI Ref ID J:182436]

Zhang W; Li YS; Nardi MA; Dang S; Yang J; Ji Y; Li Z; Karpatkin S; Wisniewski T. 2010. Dissolution of arterial platelet thrombi in vivo with a bifunctional platelet GPIIIa49-66 ligand which specifically targets the platelet thrombus. Blood 116(13):2336-44. [PubMed: 20525921]  [MGI Ref ID J:164525]

Zhang W; Nardi MA; Borkowsky W; Li Z; Karpatkin S. 2009. Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia. Blood 113(17):4086-93. [PubMed: 19023115]  [MGI Ref ID J:148441]

Zhang Y; Chen YC; Krummel MF; Rosen SD. 2012. Autotaxin through lysophosphatidic acid stimulates polarization, motility, and transendothelial migration of naive T cells. J Immunol 189(8):3914-24. [PubMed: 22962684]  [MGI Ref ID J:190533]

Zhao H; Kitaura H; Sands MS; Ross FP; Teitelbaum SL; Novack DV. 2005. Critical role of beta3 integrin in experimental postmenopausal osteoporosis. J Bone Miner Res 20(12):2116-23. [PubMed: 16294265]  [MGI Ref ID J:128133]

Zhao H; Ross FP; Teitelbaum SL. 2005. Unoccupied alpha(v)beta3 integrin regulates osteoclast apoptosis by transmitting a positive death signal. Mol Endocrinol 19(3):771-80. [PubMed: 15591537]  [MGI Ref ID J:96457]

Zou Z; Chen H; Schmaier AA; Hynes RO; Kahn ML. 2007. Structure-function analysis reveals discrete beta3 integrin inside-out and outside-in signaling pathways in platelets. Blood 109(8):3284-90. [PubMed: 17170121]  [MGI Ref ID J:145342]

Health & husbandry

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Animal Health Reports

Room Number           AX12

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

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	101045 B6129SF2/J	(approximate)
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