Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129P2 via E14TG2a ES cell line   Donating Investigator Thomas Bugge,

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

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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 (MGI Ref ID J:26874)
  • 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
  • as in wild-type mice, most of the uPA in the urine of mutant mice is in the two-chain form
• immune system phenotype
• abnormal macrophage physiology (MGI Ref ID J:26874)
  • 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
  • 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

Plaur^tm1Jld/Plaur^tm1Jld

        involves: 129P2/OlaHsd * C57BL/6

• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:63134)
  • 14 days after bleomycin treatment, wild-type and mutant mice display a similar increase in lung collagen (hydroxyproline) content
  • 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

Plaur^tm1Jld/Plaur^tm1Jld

        involves: 129P2/OlaHsd * C57BL/6J

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

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

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; UPAR; URKR; u-PAR; 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, STD PCR, vers. 3

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

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]

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]

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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