Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129P2 via E14TG2a ES cell line   Donating Investigator Dr. Thomas Bugge,   NIH/NIDCR

Appearance
black
Related Genotype: a/a

Description
Homozygous mice are born and survive to adulthood with no overt phenotypic abnormalities. No Plaur gene product (protein) is detected. In addition, activated peritoneal macrophages collected from homozygous mice fail to promote plasminogen activation in vitro. The loss of the receptor also results in a redistribution of uPA in some tissues but has no impact on pro-PLAU activation in the urogenital tract. Thus, in the absence of other challenging factors such as infection, injury, or other functional deficits, PLAUR deficiency does not compromise fertility, development, or hemostasis. These mice provide a means to test the proposed function of PLAU/PLAUR in wound repair, atherogenesis, and tumor cell invasion in vivo.

Development
This mutation was generated by replacing exon 3 with a vector containing Hprt. The 129P2-derived E14TG2a ES cell line was used.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Plaur^tm1Jld/Plaur^tm1Jld

        B6.129P2-Plaur^tm1Jld

• immune system phenotype
• chronic inflammation
  • chronic inflammation is secondary to fibrin deposition   (MGI Ref ID J:164542)
• increased inflammatory response
  • in the liver   (MGI Ref ID J:164542)
  • in the trachea of 3 in 7 mice   (MGI Ref ID J:164542)
  • however, leukocyte accumulation in standard models of inflammation is normal   (MGI Ref ID J:164542)
• • liver inflammation
    • the number of inflammatory foci is increased compared to in wild-type mice   (MGI Ref ID J:164542)
• respiratory system phenotype
• abnormal trachea morphology
  • 3 of 7 mice exhibit mild to moderate inflammation of the trachea unlike wild-type mice   (MGI Ref ID J:164542)
• liver/biliary system phenotype
• liver fibrosis   (MGI Ref ID J:164542)
• liver inflammation
  • the number of inflammatory foci is increased compared to in wild-type mice   (MGI Ref ID J:164542)
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • skin wound healing is normal   (MGI Ref ID J:164542)

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

Plaur^tm1Jld/Plaur^tm1Jld

        involves: 129P2/OlaHsd * Black Swiss

• renal/urinary system phenotype
• *normal* renal/urinary system phenotype
  • homozygotes exhibit a redistribution of urokinase plasminogen activator (uPA) in some tissues but show no changes in the accumulation or proteolytic activation of uPA in the urogenital tract   (MGI Ref ID J:26874)
  • as in wild-type mice, most of the uPA in the urine of mutant mice is in the two-chain form   (MGI Ref ID J:26874)
• immune system phenotype
• abnormal macrophage physiology
  • activated peritoneal macrophages from mutant mice fail to promote cell-surface plasminogen activation in vitro; however, homozygotes are viable, fertile and survive to adulthood with no apparent anatomical defects   (MGI Ref ID J:26874)
  • also, homozygotes that are unchallenged by disease, infection or injury show no pathological lesions or hepatic fibrin deposits up to 6-8 months of age   (MGI Ref ID J:26874)

Plaur^tm1Jld/Plaur^tm1Jld

        involves: 129P2/OlaHsd * C57BL/6

• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • 14 days after bleomycin treatment, wild-type and mutant mice display a similar increase in lung collagen (hydroxyproline) content   (MGI Ref ID J:63134)
  • 14 days after bleomycin treatment, wild-type and mutant mice show similar focal areas of pulmonary fibrosis surrounded by normal alveoli; no intra-alveolar hemorrhage or early deaths are observed   (MGI Ref ID J:63134)

Plaur^tm1Jld/Plaur^tm1Jld

        involves: 129P2/OlaHsd * C57BL/6J

• cardiovascular system phenotype
• decreased angiogenesis
  • aortic vessel explants show a reduced rate of sprouting (2/3 of controls) in collagen lattices   (MGI Ref ID J:108675)

View Research Applications

Research Applications

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

Plaur^tm1Jld related

Hematological Research
Clotting Defects

Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Plaurtm1Jld
Allele Name		targeted mutation 1, Jay L Degen
Allele Type		Targeted (knock-out)
Common Name(s)		Plaurtm1; uPAR-;
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Plaur, plasminogen activator, urokinase receptor
Chromosome		7
Gene Common Name(s)		CD87; Par; Plaur3; U-PAR; UPAR; URKR; uPAR-2; uPAR-3; urokinase-type plasminogen activator receptor;
Molecular Note		Exon 3, encoding the second half of the amino-terminal uPA binding domain, was replaced by an HPRT minigene. [MGI Ref ID J:26874]

Genotyping

Genotyping Information

Genotyping Protocols

Plaur^tm1Jld, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bugge TH; Suh TT; Flick MJ; Daugherty CC; Romer J; Solberg H; Ellis V; Dano K; Degen JL. 1995. The receptor for urokinase-type plasminogen activator is not essential for mouse development or fertility. J Biol Chem 270(28):16886-94. [PubMed: 7622505]  [MGI Ref ID J:26874]

Additional References

Bugge TH; Kombrinck KW; Flick MJ; Daugherty CC; Danton MJ; Degen JL. 1996. Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency. Cell 87(4):709-19. [PubMed: 8929539]  [MGI Ref ID J:36591]

Ling Q; Jacovina AT; Deora A; Febbraio M; Simantov R; Silverstein RL; Hempstead B; Mark WH; Hajjar KA. 2004. Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo. J Clin Invest 113(1):38-48. [PubMed: 14702107]  [MGI Ref ID J:87621]

Ong K; Horsfall W; Conway EM; Schuh AC. 2000. Early embryonic expression of murine coagulation system components. Thromb Haemost 84(6):1023-30. [PubMed: 11154109]  [MGI Ref ID J:74089]

Piguet PF; Da Laperrousaz C; Vesin C; Tacchini-Cottier F; Senaldi G; Grau GE. 2000. Delayed mortality and attenuated thrombocytopenia associated with severe malaria in urokinase- and urokinase receptor-deficient mice. Infect Immun 68(7):3822-9. [PubMed: 10858190]  [MGI Ref ID J:62841]

Solberg H; Rinkenberger J; Dano K; Werb Z; Lund LR. 2003. A functional overlap of plasminogen and MMPs regulates vascularization during placental development. Development 130(18):4439-50. [PubMed: 12900459]  [MGI Ref ID J:84595]

Swaisgood CM; French EL; Noga C; Simon RH; Ploplis VA. 2000. The development of bleomycin-induced pulmonary fibrosis in mice deficient for components of the fibrinolytic system. Am J Pathol 157(1):177-87. [PubMed: 10880388]  [MGI Ref ID J:63134]

Plaur^tm1Jld related

Brodsky S; Chen J; Lee A; Akassoglou K; Norman J; Goligorsky MS. 2001. Plasmin-dependent and -independent effects of plasminogen activators and inhibitor-1 on ex vivo angiogenesis. Am J Physiol Heart Circ Physiol 281(4):H1784-92. [PubMed: 11557572]  [MGI Ref ID J:108675]

Bryer SC; Fantuzzi G; Van Rooijen N; Koh TJ. 2008. Urokinase-type plasminogen activator plays essential roles in macrophage chemotaxis and skeletal muscle regeneration. J Immunol 180(2):1179-88. [PubMed: 18178858]  [MGI Ref ID J:130940]

Bryer SC; Koh TJ. 2007. The urokinase-type plasminogen activator receptor is not required for skeletal muscle inflammation or regeneration. Am J Physiol Regul Integr Comp Physiol 293(3):R1152-8. [PubMed: 17567716]  [MGI Ref ID J:143827]

Bugge TH; Flick MJ; Danton MJ; Daugherty CC; Romer J; Dano K; Carmeliet P; Collen D; Degen JL. 1996. Urokinase-type plasminogen activator is effective in fibrin clearance in the absence of its receptor or tissue-type plasminogen activator. Proc Natl Acad Sci U S A 93(12):5899-904. [PubMed: 8650190]  [MGI Ref ID J:134773]

Connolly BM; Choi EY; Gardsvoll H; Bey AL; Currie BM; Chavakis T; Liu S; Molinolo A; Ploug M; Leppla SH; Bugge TH. 2010. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation. Blood 116(9):1593-603. [PubMed: 20466854]  [MGI Ref ID J:164542]

DiPasquale DM; Cheng M; Billich W; Huang SA; van Rooijen N; Hornberger TA; Koh TJ. 2007. Urokinase-type plasminogen activator and macrophages are required for skeletal muscle hypertrophy in mice. Am J Physiol Cell Physiol 293(4):C1278-85. [PubMed: 17652428]  [MGI Ref ID J:145128]

Farris SD; Hu JH; Krishnan R; Emery I; Chu T; Du L; Kremen M; Dichek HL; Gold E; Ramsey SA; Dichek DA. 2011. Mechanisms of urokinase plasminogen activator (uPA)-mediated atherosclerosis: role of the uPA receptor and S100A8/A9 proteins. J Biol Chem 286(25):22665-77. [PubMed: 21536666]  [MGI Ref ID J:174810]

Higazi AA; El-Haj M; Melhem A; Horani A; Pappo O; Alvarez CE; Muhanna N; Friedman SL; Safadi R. 2008. Immunomodulatory effects of plasminogen activators on hepatic fibrogenesis. Clin Exp Immunol 152(1):163-73. [PubMed: 18279442]  [MGI Ref ID J:133582]

Hovius JW; Bijlsma MF; van der Windt GJ; Wiersinga WJ; Boukens BJ; Coumou J; Oei A; de Beer R; de Vos AF; van 't Veer C; van Dam AP; Wang P; Fikrig E; Levi MM; Roelofs JJ; van der Poll T. 2009. The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. PLoS Pathog 5(5):e1000447. [PubMed: 19461880]  [MGI Ref ID J:162185]

Kenny S; Gamble J; Lyons S; Vlatkovic N; Dimaline R; Varro A; Dockray GJ. 2013. Gastric expression of plasminogen activator inhibitor (PAI)-1 is associated with hyperphagia and obesity in mice. Endocrinology 154(2):718-26. [PubMed: 23254194]  [MGI Ref ID J:194605]

LaRusch GA; Mahdi F; Shariat-Madar Z; Adams G; Sitrin RG; Zhang WM; McCrae KR; Schmaier AH. 2010. Factor XII stimulates ERK1/2 and Akt through uPAR, integrins, and the EGFR to initiate angiogenesis. Blood 115(24):5111-20. [PubMed: 20228268]  [MGI Ref ID J:161559]

Lund IK; Nielsen BS; Almholt K; Rono B; Hald A; Illemann M; Green KA; Christensen IJ; Romer J; Lund LR. 2011. Concomitant lack of MMP9 and uPA disturbs physiological tissue remodeling. Dev Biol 358(1):56-67. [PubMed: 21802414]  [MGI Ref ID J:176606]

May AE; Kanse SM; Lund LR; Gisler RH; Imhof BA; Preissner KT. 1998. Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo. J Exp Med 188(6):1029-37. [PubMed: 9743521]  [MGI Ref ID J:112020]

Nassar T; Haj-Yehia A; Akkawi S; Kuo A; Bdeir K; Mazar A; Cines DB; Higazi AA. 2002. Binding of urokinase to low density lipoprotein-related receptor (LRP) regulates vascular smooth muscle cell contraction. J Biol Chem 277(43):40499-504. [PubMed: 12171938]  [MGI Ref ID J:118782]

Nassar T; Yarovoi S; Fanne RA; Akkawi S; Jammal M; Allen TC; Idell S; Cines DB; Higazi AA. 2010. Regulation of airway contractility by plasminogen activators through N-methyl-D-aspartate receptor-1. Am J Respir Cell Mol Biol 43(6):703-11. [PubMed: 20097831]  [MGI Ref ID J:179956]

Renckens R; Pater JM; van der Poll T. 2006. Plasminogen activator inhibitor type-1-deficient mice have an enhanced IFN-gamma response to lipopolysaccharide and staphylococcal enterotoxin B. J Immunol 177(11):8171-6. [PubMed: 17114493]  [MGI Ref ID J:140679]

Roelofs JJ; Rouschop KM; Teske GJ; Claessen N; Weening JJ; van der Poll T; Florquin S. 2006. The urokinase plasminogen activator receptor is crucially involved in host defense during acute pyelonephritis. Kidney Int 70(11):1942-7. [PubMed: 17035942]  [MGI Ref ID J:136481]

Sato J; Schorey J; Ploplis VA; Haalboom E; Krahule L; Castellino FJ. 2003. The fibrinolytic system in dissemination and matrix protein deposition during a mycobacterium infection. Am J Pathol 163(2):517-31. [PubMed: 12875972]  [MGI Ref ID J:113588]

Stempien-Otero A; Plawman A; Meznarich J; Dyamenahalli T; Otsuka G; Dichek DA. 2006. Mechanisms of cardiac fibrosis induced by urokinase plasminogen activator. J Biol Chem 281(22):15345-51. [PubMed: 16554301]  [MGI Ref ID J:113474]

Swaisgood CM; French EL; Noga C; Simon RH; Ploplis VA. 2000. The development of bleomycin-induced pulmonary fibrosis in mice deficient for components of the fibrinolytic system. Am J Pathol 157(1):177-87. [PubMed: 10880388]  [MGI Ref ID J:63134]

Uchida HA; Poduri A; Subramanian V; Cassis LA; Daugherty A. 2011. Urokinase-type plasminogen activator deficiency in bone marrow-derived cells augments rupture of angiotensin II-induced abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 31(12):2845-52. [PubMed: 21868698]  [MGI Ref ID J:191466]

van Zoelen MA; Florquin S; de Beer R; Pater JM; Verstege MI; Meijers JC; van der Poll T. 2009. Urokinase plasminogen activator receptor-deficient mice demonstrate reduced hyperoxia-induced lung injury. Am J Pathol 174(6):2182-9. [PubMed: 19435793]  [MGI Ref ID J:148762]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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