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 BALB/c Donor Strain 129S2 via D3 ES cell line   Donating Investigator Peter Carmeliet,   University of Leuven

Description
Homozygotes develop normally, are fertile and have a normal life span. Rectal prolapse of a non-infectious origin develops in 9% of homozygotes and/or extensive non-healing ulcerations occur at the eyelids and around the face. Small, focal fibrin deposits are occasionally seen in the intestines and in the sinusoids of the liver, and excessive fibrin deposits are seen in ulcerated skin or prolapsed rectum. Pulmonary clot lysis is comparable to that seen in normal wildtype siblings. Endotoxin induced venous thrombosis is increased over normal wildtype siblings. Fibrin dissolution by PLAU-deficient macrophages is greatly reduced but macrophage invasion into the peritoneal cavity after thioglycollate injection is unaffected. Homozygous knockout mice have increased levels of Abeta42 and Abeta40 in plasma. Brain Abeta levels are not significantly different than controls. In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Plau^tm1Mlg allele

002509	B6.129S2-Plautm1Mlg/J
002329	FVB.129S2-Plautm1Mlg/J

View Strains carrying   Plau^tm1Mlg     (2 strains)

Additional Web Information

Congenic Nomenclature
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Alzheimer Disease; AD - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

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.

Plau^tm1Mlg/Plau^tm1Mlg

        involves: 129S2/SvPas * C57BL/6

• life span-post-weaning/aging
• *normal* life span-post-weaning/aging (MGI Ref ID J:17427)
  • homozygotes display a normal lifespan relative to wild-type mice
• growth/size phenotype
• *normal* growth/size phenotype (MGI Ref ID J:17427)
  • at 5 weeks of age, homozygotes exhibit a normal body weight relative to wild-type mice
• cardiovascular system phenotype
• cardiac interstitial fibrosis (MGI Ref ID J:95236)
  • in response to pressure overload, homozygotes show only minimal signs of maladaptation (i.e. myolysis, fibrosis or increased intercapillary distance) relative to wild-type mice
• increased resistance to induced choroidal neovascularization (MGI Ref ID J:82604)
  • in response to laser-induced injury of the Bruch's membrane, homozygotes display almost complete absence of choroidal neovascularization (CNV) at the site of trauma; in contrast, wild-type mice show a robust neovascular reaction
  • resistance to CNV is associated with excessive fibrinogen-fibrin deposition at the site of choroidal trauma and in retinal vessels
• increased ventricle muscle contractility (MGI Ref ID J:95236)
  • at 7 weeks after TAB, homozygotes exhibit increased LV contractility, indicating normal fractional shortening with no cardiac failure or pulmonary congestion
• left ventricle hypertrophy (MGI Ref ID J:95236)
  • after transverse aortic banding (TAB), i.e. acute pressure overload, homozygotes remain significantly protected against LV hypertrophy for at least 7 weeks
  • homozygotes display only a 20% increase in LV/body ratio and only a 22% increase in LV cardiomyocyte size relative to wild-type (~35% and ~40%, respectively)
  • at 7 weeks after TAB, LV systolic dysfunction and dilatation are only marginally detectable without signs of pulmonary edema
• digestive/alimentary phenotype
• rectal prolapse (MGI Ref ID J:17427)
  • at ~22 weeks of age, 9% of homozygotes display rectal prolapse of a non-infectious origin
• hearing/vestibular/ear phenotype
• abnormal outer ear morphology (MGI Ref ID J:17427)
  • at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the ear tag and the face
• hematopoietic system phenotype
• *normal* hematopoietic system phenotype (MGI Ref ID J:17427)
  • homozygotes exhibit normal spontaneous lysis of a 125I-fibrin-labeled pulmonary plasma clot relative to wild-type
• increased lymphocyte cell number (MGI Ref ID J:63134)
  • at day 7 post-treatment, the decline in macrophage counts coincides with an increase in the percentage of lymphocytes found in the lungs of bleomycin-treated mice
• immune system phenotype
• abnormal cell-mediated immunity (MGI Ref ID J:87817)
  • homozygotes fail to generate a type 2 immune response following schistosomal antigen challenge
  • in response to schistosomal egg antigen (SEA), homozygotes fail to develop a delayed-type hypersensitivity response to SEA, do not polarize Ig production to IgE, fail to produce high levels of IL-4, IL-5, or IL-13 and generate pulmonary granulomas that are deficient in eosinophils
  • homozygotes fail to generate a type 1 immune response in the lung during pulmonary fungal infection with C. neoformans
  • in response to C. neoformans infection, homozygotes show impaired T cell proliferation in regional lymph nodes and fail to produce high levels of T1 cytokines (IFN-gamma and IL-12) in the lung; instead, mutants exhibit increased levels of IL-5, a T2 cytokine
• abnormal macrophage physiology (MGI Ref ID J:17427)
  • in contrast to wild-type, homozygotes exhibit no plasminogen-dependent breakdown of 125I-fibrin-labeled matrix and of 3H-proline-labeled subendothelial breakdown by thioglycollate-activated macrohages; invasion of macrophages into the peritoneal cavity remains unaffected
• impaired macrophage recruitment (MGI Ref ID J:63134)
  • 5 days after bleomycin treatment, homozygotes display a peak in lung macrophage levels that coincides with the peak time observed in wild-type mice; however, their marcophage levels are significantly reduced relative to wild-type
  • 7 days after bleomycin treatment, mutant and wild-type mice show a similar decrease in the number and percentage of macrophages found in the lung
• abnormal neutrophil physiology (MGI Ref ID J:75573)
  • 48 hours after intranasal inoculation with S. pneumoniae, homozygotes exhibit an enhanced antibacterial host defense, with less pneumococci in their lungs and increased neutrophil influx in the bronchoalveolar lavage fluid but no reduction in mortality relative to wild-type
  • relative to wild-type, purified neutrophils from mutant mice exhibit a ~50% reduction in superoxide production in response to fMLP (a potent chemotaxin and activator of neutrophils) across the entire dose range tested; repletion with murine uPA completely reverses the defect in superoxide generation
  • in response to fMLP, mutant neutrophils exhibit reduced neutrophil exocytosis of azurophilic granules (as shown by reduced myeloperoxidase release); however, this defect is not corrected by repletion with extracellular uPA
  • in contrast, mutant neutrophils show normal agonist-stimulated release of specific granules relative to wild-type neutrophils
• impaired neutrophil phagocytosis (MGI Ref ID J:91980)
  • in vitro, purified neutrophils from mutant mice exhibit a significant reduction in phagocytosis of E. coli at all time points; repletion with murine uPA substantially reverses the defect in neutrophil phagocytosis
• impaired granulocyte bactericidal activity (MGI Ref ID J:91980)
  • in vitro, purified neutrophils from mutant mice display significant defects in several aspects of the antibacterial neutrophil activation process that lead to E. coli killing and effective host defense
• abnormal fibrinogen physiology (MGI Ref ID J:63134)
  • bleomycin-treated homozygotes exhibit extensive areas of fibrin(ogen) deposition in the lung interstitium which are associated with areas of fibrosis
  • after laser-induced injury of the Bruch's membrane, homozygotes show massive accumulation of fibrinogen-fibrin both in the retinal vessels, and in the bottom of the laser-induced trauma
• increased lymphocyte cell number (MGI Ref ID J:63134)
  • at day 7 post-treatment, the decline in macrophage counts coincides with an increase in the percentage of lymphocytes found in the lungs of bleomycin-treated mice
• increased susceptibility to fungal infection (MGI Ref ID J:95637)
  • 21 days after inoculation with Cryptococcus neoformans, homozygotes contain significantly higher lung CFUs than wild-type mice
  • C. neoformans-infected mutants disseminate the fungal pathogen to their spleen; eventually 15 out of 19 mutants (versus 3/19 wild-type) die from fungal meningitis
• increased susceptibility to parasitic infection (MGI Ref ID J:87817)
  • when primed homozygotes are challenged with schistosomal egg antigen (SEA) they exhibit a severe immune defect in response to this T2-eliciting antigen
• muscle phenotype
• increased ventricle muscle contractility (MGI Ref ID J:95236)
  • at 7 weeks after TAB, homozygotes exhibit increased LV contractility, indicating normal fractional shortening with no cardiac failure or pulmonary congestion
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:17427)
  • homozygotes display normal litter size and frequency of litters relative to wild-type mice
• respiratory system phenotype
• pulmonary interstitial fibrosis (MGI Ref ID J:63134)
  • 14 days after bleomycin treatment, homozygotes exhibit an increase in lung hydroxyproline (collagen) content that is comparable to that observed in bleomycin-treated wild-type mice
  • histological analysis 14 days after lung injury indicates extensive interstitial fibrosis in mutant mice relative to wild-type; however, no hemorrhage or extensive collagen deposition is observed
  • 62% of bleomycin-treated homozygotes die as early as ~7 days after treatment, possibly as a result of extensive fibrosis
• vision/eye phenotype
• abnormal eyelid morphology (MGI Ref ID J:17427)
  • at ~26 weeks of age, 5% homozygotes display severe non-healing ulcerations at the eyelids
• increased resistance to induced choroidal neovascularization (MGI Ref ID J:82604)
  • in response to laser-induced injury of the Bruch's membrane, homozygotes display almost complete absence of choroidal neovascularization (CNV) at the site of trauma; in contrast, wild-type mice show a robust neovascular reaction
  • resistance to CNV is associated with excessive fibrinogen-fibrin deposition at the site of choroidal trauma and in retinal vessels
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:55243)
  • homozygotes subjected to focal cerebral ischemia induced by persistent occlusion of the left middle cerebral artery produce an infarct with a size that is comparable to that produced in wild-type mice
• homeostasis/metabolism phenotype
• abnormal circulating protein level (MGI Ref ID J:104962)
  • 3-6 month-old mice have elevated levels of plasma amyloid beta 42 (Abeta42) and Abeta40; by 11 months of age, difference in levels between mutants and controls has increased significantly
• abnormal fibrinogen physiology (MGI Ref ID J:63134)
  • bleomycin-treated homozygotes exhibit extensive areas of fibrin(ogen) deposition in the lung interstitium which are associated with areas of fibrosis
  • after laser-induced injury of the Bruch's membrane, homozygotes show massive accumulation of fibrinogen-fibrin both in the retinal vessels, and in the bottom of the laser-induced trauma
• thrombosis (MGI Ref ID J:17427)
  • homozygotes occasionally exhibit small, focal fibrin deposits in the intestines and in the sinusoids of the liver and extensive fibrin deposits in the ulcerated skin, ear or prolapsed rectum
  • in response to injection of pro-inflammatory endotoxin in the footpad, homozygotes exhibit overt venous thrombosis at a significantly higher incidence (90% versus 54%) and to a much larger extent than wild-type mice (60% of mutants show >4 thrombosed veins per tissue section versus only 15% in wild-type)
• craniofacial phenotype
• abnormal outer ear morphology (MGI Ref ID J:17427)
  • at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the ear tag and the face
• other phenotype
• *normal* other phenotype (MGI Ref ID J:104962)
  • Abeta40 and 42 levels are not increased in mutant brains relative to controls

Plau^tm1Mlg/Plau^tm1Mlg

        either: B6.Cg-Plau^tm1Mlg or (involves: Black Swiss * C57BL/6)

• homeostasis/metabolism phenotype
• reduced thrombolysis (MGI Ref ID J:64220)
  • in a model of pulmonary microembolism, wild-type mice are able to clear 125I-microemboli rapidly with complete lysis by 5 hours; in contrast, mutants remain unable to lyse pulmonary microemboli throughout the 5-hr experimental period
  • in these mutants, impaired fibrinolysis can be rescued completely by providing urokinase exogenously

Plau^tm1Mlg/Plau^tm1Mlg

        B6.Cg-Plau^tm1Mlg

• tumorigenesis
• altered tumor morphology (MGI Ref ID J:65383)
  • 3 weeks after implantation of T241 fibrosarcoma cells, primary tumors from mutant mice appear to be better delineated and less hemorrhagic than tumors from wild-type mice
  • also, tumors from mutant mice show an increase in collagen deposition at the periphery of the lesion, forming a fibrous and thick pseudocapsule that is almost undetectable in tumors from wild-type mice
  • ultrastructurally, fibrosarcoma tumor neovessels formed in mutant mice are larger and less mature than tumor vessels from wild-type mice
• decreased tumor growth/size (MGI Ref ID J:65383)
  • 3 weeks after implantation of T241 fibrosarcoma cells, primary tumors from mutant mice are significantly smaller than tumors from wild-type mice
  • consistent with tumor growth suppression, tumor tissues from mutant mice exhibit lower proliferative and higher apoptotic indices relative to tumor tissues from wild-type mice
• decreased metastatic potential (MGI Ref ID J:65383)
  • following implantation of T241 fibrosarcoma cells, only a limited number of mutants develop metastatic lesions in the lung and brain; in contrast, almost all of wild-type mice display metastases to the same locations
  • notably, only mutants that survive for longer periods (2 months) after the injection develop these lesions, indicating a delay in metastasis
• digestive/alimentary phenotype
• abnormal perineum morphology (MGI Ref ID J:73613)
  • in males with rectal prolapse, the perineal region is swollen on both sides of the evaginated rectal mucosa
• abnormal rectum morphology (MGI Ref ID J:73613)
  • in males with rectal prolapse, the rectal mucosa is exteriorized and evaginated
• rectal prolapse (MGI Ref ID J:73613)
  • starting at 6 months, male (but not female) homozygotes show a high incidence of rectal prolapse
  • in mutant males, rectal prolapse is irreducible and completely exteriorized by 12 months
• endocrine/exocrine gland phenotype
• herniated seminal glands (MGI Ref ID J:73613)
  • males with rectal prolapse develop an irreducible hernia of the seminal vesicles through the pelvic outlet and through a hiatus found between the iliococcygeus (ISC), the bulbocavrnosus (BC), and the tail
  • this hernia results in chronic stretching and thinning of the ISC, BC, and levator ani (LA) pelvic floor muscles
• immune system phenotype
• abnormal cytokine level (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in interleukin-1beta levels in the synovium relative to wild-type
  • in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in TNF levels in the synovium relative to wild-type
• abnormal fibrinogen physiology (MGI Ref ID J:68083)
  • at 9 days after glycerol-induced injury of skeletal muscles, homozygotes exhibit abundant fibrin deposits in degenerating muscle fibers
• decreased T cell proliferation (MGI Ref ID J:75303)
  • despite a normal antibody response to type II collagen, T cells from arthritic homozygotes show a reduced proliferative response and produce less interferon-gamma on antigen stimulation in vitro
• decreased inflammatory response (MGI Ref ID J:68083)
  • in response to glycerol-induced muscle degeneration, homozygotes display significantly reduced numbers of macrophages and neutrophils at the site of injury relative to wild-type
• decreased susceptibility to induced arthritis (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, homozygotes develop a significantly milder disease than wild-type mice, with little inflammation and joint destruction
  • in this chronic systemic model, the affected limbs of mutants are rigid but not swollen; arthritis is largely confined to the ankle joint, with most joints in the feet appearing normal
  • surprisingly, the joints of arthritic homozygotes display minimal fibrin(ogen) deposition relative to wild-type
• impaired macrophage recruitment (MGI Ref ID J:68083)
  • in response to skeletal muscle degeneration, homozygotes display a 50% reduction in macrophage recruitment at the injury site 48 hours after glycerol-induced injury
• muscle phenotype
• abnormal muscle regeneration (MGI Ref ID J:68083)
  • in response to glycerol-induced injury, homozygotes exhibit a severe skeletal muscle regeneration defect relative to wild-type; this defect is apparent at 5 days but is most striking at 9 and 20 days after injury
  • at 5 days after injury, skeletal muscles from mutant mice appear edematous; in contrast to wild-type, no uninucleated, small myofibers are yet formed
  • at 7 days after injury, most injured skeletal muscles appear necrotic and show extensive fibrosis
  • at 9 and 20 days, numerous degenerated myotubes and fibrosis are still visible in mutant muscles whereas no signs of previous damage are detectable in wild-type muscles
  • systemic fibrinogen depletion via ancrod administration restores muscle regeneration: 9 days after injury, ancrod-treated mutants exhibit improved muscle regeneration, with centrally located nuclei inside the regenerated fibers
• myopathy (MGI Ref ID J:73613)
  • males with rectal prolapse, exhibit myopathic damage in the affected pelvic floor muscles (ISC, BC and LA)
  • most affected myofibers have centrally located nuclei; some show basophilic degeneration in the absence of denervation, fibrosis or inflammation
• reproductive system phenotype
• abnormal perineum morphology (MGI Ref ID J:73613)
  • in males with rectal prolapse, the perineal region is swollen on both sides of the evaginated rectal mucosa
• herniated seminal glands (MGI Ref ID J:73613)
  • males with rectal prolapse develop an irreducible hernia of the seminal vesicles through the pelvic outlet and through a hiatus found between the iliococcygeus (ISC), the bulbocavrnosus (BC), and the tail
  • this hernia results in chronic stretching and thinning of the ISC, BC, and levator ani (LA) pelvic floor muscles
• skeleton phenotype
• decreased susceptibility to induced arthritis (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, homozygotes develop a significantly milder disease than wild-type mice, with little inflammation and joint destruction
  • in this chronic systemic model, the affected limbs of mutants are rigid but not swollen; arthritis is largely confined to the ankle joint, with most joints in the feet appearing normal
  • surprisingly, the joints of arthritic homozygotes display minimal fibrin(ogen) deposition relative to wild-type
• homeostasis/metabolism phenotype
• abnormal cytokine level (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in interleukin-1beta levels in the synovium relative to wild-type
  • in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in TNF levels in the synovium relative to wild-type
• abnormal fibrinogen physiology (MGI Ref ID J:68083)
  • at 9 days after glycerol-induced injury of skeletal muscles, homozygotes exhibit abundant fibrin deposits in degenerating muscle fibers
• hematopoietic system phenotype
• decreased T cell proliferation (MGI Ref ID J:75303)
  • despite a normal antibody response to type II collagen, T cells from arthritic homozygotes show a reduced proliferative response and produce less interferon-gamma on antigen stimulation in vitro

View Research Applications

Research Applications

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

Plau^tm1Mlg related

Hematological Research
Clotting Defects

Metabolism Research

Neurobiology Research
Alzheimer's Disease

Genes & Alleles

Gene & Allele Information

Allele Symbol		Plautm1Mlg
Allele Name		targeted mutation 1, Richard C Mulligan
Allele Type		Targeted (knock-out)
Common Name(s)		UPA-; u-PA-;
Mutation Made By		Peter Carmeliet,   University of Leuven
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Plau, plasminogen activator, urokinase
Chromosome		14
Gene Common Name(s)		ATF; MGC124931; UPA; UPAM; URK; UROKINASE; u-PA; urokinase-type plasminogen activator;
Molecular Note		The gene was disrupted using neomycin resistance cassette. The vector replaced genomic sequences encompassing all but 23 amino acids of the coding sequence. Targeting was confirmed by the absence of gene specific mRNA and immunoreactivity. [MGI Ref ID J:17427]

Genotyping

Genotyping Information

Genotyping Protocols

Plau^tm1, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Carmeliet P; Schoonjans L; Kieckens L; Ream B; Degen J; Bronson R; De Vos R; van den Oord JJ; Collen D; Mulligan RC. 1994. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 368(6470):419-24. [PubMed: 8133887]  [MGI Ref ID J:17427]

Additional References

Dewerchin M; Nuffelen AV; Wallays G; Bouche A; Moons L; Carmeliet P; Mulligan RC; Collen D. 1996. Generation and characterization of urokinase receptor-deficient mice. J Clin Invest 97(3):870-8. [PubMed: 8609247]  [MGI Ref ID J:31253]

Plau^tm1Mlg related

Abraham E; Gyetko MR; Kuhn K; Arcaroli J; Strassheim D; Park JS; Shetty S; Idell S. 2003. Urokinase-type plasminogen activator potentiates lipopolysaccharide-induced neutrophil activation. J Immunol 170(11):5644-51. [PubMed: 12759445]  [MGI Ref ID J:131136]

Bdeir K; Murciano JC; Tomaszewski J; Koniaris L; Martinez J; Cines DB; Muzykantov VR; Higazi AA. 2000. Urokinase mediates fibrinolysis in the pulmonary microvasculature Blood 96(5):1820-6. [PubMed: 10961882]  [MGI Ref ID J:64220]

Bergers G; Brekken R; McMahon G; Vu TH; Itoh T; Tamaki K; Tanzawa K; Thorpe P; Itohara S; Werb Z; Hanahan D. 2000. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis Nat Cell Biol 2(10):737-44. [PubMed: 11025665]  [MGI Ref ID J:65019]

Bezerra JA; Currier AR; Melin-Aldana H; Sabla G; Bugge TH; Kombrinck KW; Degen JL. 2001. Plasminogen activators direct reorganization of the liver lobule after acute injury. Am J Pathol 158(3):921-9. [PubMed: 11238040]  [MGI Ref ID J:114282]

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]

Carmeliet P; Moons L; Dewerchin M; Rosenberg S; Herbert JM; Lupu F; Collen D. 1998. Receptor-independent role of urokinase-type plasminogen activator in pericellular plasmin and matrix metalloproteinase proteolysis during vascular wound healing in mice. J Cell Biol 140(1):233-45. [PubMed: 9425170]  [MGI Ref ID J:45379]

Carmeliet P; Moons L; Herbert JM; Crawley J; Lupu F; Lijnen R; Collen D. 1997. Urokinase but not tissue plasminogen activator mediates arterial neointima formation in mice. Circ Res 81(5):829-39. [PubMed: 9351457]  [MGI Ref ID J:95503]

Carmeliet P; Moons L; Lijnen R; Baes M; Lemaitre V; Tipping P; Drew A; Eeckhout Y; Shapiro S; Lupu F; Collen D. 1997. Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet 17(4):439-44. [PubMed: 9398846]  [MGI Ref ID J:44387]

Christie PD; Edelberg JM; Picard MH; Foulkes AS; Mamuya W; Weiler-Guettler H; Rubin RH; Gilbert P; Rosenberg RD. 1999. A murine model of myocardial microvascular thrombosis. J Clin Invest 104(5):533-9. [PubMed: 10487767]  [MGI Ref ID J:57461]

Cook AD; Braine EL; Campbell IK; Hamilton JA. 2002. Differing roles for urokinase and tissue-type plasminogen activator in collagen-induced arthritis. Am J Pathol 160(3):917-26. [PubMed: 11891190]  [MGI Ref ID J:75303]

Daci E; Everts V; Torrekens S; Van Herck E; Tigchelaar-Gutterr W; Bouillon R; Carmeliet G. 2003. Increased bone formation in mice lacking plasminogen activators. J Bone Miner Res 18(7):1167-76. [PubMed: 12854826]  [MGI Ref ID J:111454]

Deindl E; Ziegelhoffer T; Kanse SM; Fernandez B; Neubauer E; Carmeliet P; Preissner KT; Schaper W. 2003. Receptor-independent role of the urokinase-type plasminogen activator during arteriogenesis. FASEB J 17(9):1174-6. [PubMed: 12692088]  [MGI Ref ID J:118013]

Deng GG; Martin-McNulty B; Sukovich DA; Freay A; Halks-Miller M; Thinnes T; Loskutoff DJ; Carmeliet P; Dole WP; Wang YX. 2003. Urokinase-type plasminogen activator plays a critical role in angiotensin II-induced abdominal aortic aneurysm. Circ Res 92(5):510-7. [PubMed: 12600880]  [MGI Ref ID J:115512]

Ertekin-Taner N; Ronald J; Feuk L; Prince J; Tucker M; Younkin L; Hella M; Jain S; Hackett A; Scanlin L; Kelly J; Kihiko-Ehman M; Neltner M; Hersh L; Kindy M; Markesbery W; Hutton M; de Andrade M; Petersen RC; Graff-Radford N; Estus S; Brookes AJ; Younkin SG. 2005. Elevated amyloid beta protein (Abeta42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator gene. Hum Mol Genet 14(3):447-60. [PubMed: 15615772]  [MGI Ref ID J:104962]

Gueler F; Rong S; Mengel M; Park JK; Kiyan J; Kirsch T; Dumler I; Haller H; Shushakova N. 2008. Renal urokinase-type plasminogen activator (uPA) receptor but not uPA deficiency strongly attenuates ischemia reperfusion injury and acute kidney allograft rejection. J Immunol 181(2):1179-89. [PubMed: 18606671]  [MGI Ref ID J:137466]

Gutierrez LS; Schulman A; Brito-Robinson T; Noria F; Ploplis VA; Castellino FJ. 2000. Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1 Cancer Res 60(20):5839-47. [PubMed: 11059781]  [MGI Ref ID J:65383]

Gyetko MR; Aizenberg D; Mayo-Bond L. 2004. Urokinase-deficient and urokinase receptor-deficient mice have impaired neutrophil antimicrobial activation in vitro. J Leukoc Biol 76(3):648-56. [PubMed: 15240745]  [MGI Ref ID J:91980]

Gyetko MR; Chen GH; McDonald RA; Goodman R; Huffnagle GB; Wilkinson CC; Fuller JA; Toews GB. 1996. Urokinase is required for the pulmonary inflammatory response to Cryptococcus neoformans. A murine transgenic model. J Clin Invest 97(8):1818-26. [PubMed: 8621764]  [MGI Ref ID J:95637]

Gyetko MR; Libre EA; Fuller JA; Chen GH; Toews G. 1999. Urokinase is required for T lymphocyte proliferation and activation in vitro. J Lab Clin Med 133(3):274-88. [PubMed: 10072260]  [MGI Ref ID J:53238]

Gyetko MR; Sud S; Chen GH; Fuller JA; Chensue SW; Toews GB. 2002. Urokinase-type plasminogen activator is required for the generation of a type 1 immune response to pulmonary Cryptococcus neoformans infection. J Immunol 168(2):801-9. [PubMed: 11777975]  [MGI Ref ID J:95638]

Gyetko MR; Sud S; Chensue SW. 2004. Urokinase-deficient mice fail to generate a type 2 immune response following schistosomal antigen challenge. Infect Immun 72(1):461-7. [PubMed: 14688127]  [MGI Ref ID J:87817]

Gyetko MR; Sud S; Kendall T; Fuller JA; Newstead MW; Standiford TJ. 2000. Urokinase receptor-deficient mice have impaired neutrophil recruitment in response to pulmonary Pseudomonas aeruginosa infection. J Immunol 165(3):1513-9. [PubMed: 10903758]  [MGI Ref ID J:110728]

Heymans S; Lupu F; Terclavers S; Vanwetswinkel B; Herbert JM; Baker A; Collen D; Carmeliet P; Moons L. 2005. Loss or inhibition of uPA or MMP-9 attenuates LV remodeling and dysfunction after acute pressure overload in mice. Am J Pathol 166(1):15-25. [PubMed: 15631996]  [MGI Ref ID J:95236]

Heymans S; Luttun A; Nuyens D; Theilmeier G; Creemers E; Moons L; Dyspersin GD; Cleutjens JP; Shipley M; Angellilo A; Levi M; Nube O; Baker A; Keshet E; Lupu F; Herbert JM; Smits JF; Shapiro SD; Baes M; Borgers M; Collen D; Daemen MJ; Carmeliet P. 1999. Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med 5(10):1135-42. [PubMed: 10502816]  [MGI Ref ID J:124004]

Heymans S; Pauschinger M; De Palma A; Kallwellis-Opara A; Rutschow S; Swinnen M; Vanhoutte D; Gao F; Torpai R; Baker AH; Padalko E; Neyts J; Schultheiss HP; Van de Werf F; Carmeliet P; Pinto YM. 2006. Inhibition of urokinase-type plasminogen activator or matrix metalloproteinases prevents cardiac injury and dysfunction during viral myocarditis. Circulation 114(6):565-73. [PubMed: 16880329]  [MGI Ref ID J:123852]

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]

Kawasaki T; Dewerchin M; Lijnen HR; Vermylen J; Hoylaerts MF. 2000. Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during acute arterial thrombosis in mice. Blood 96(1):153-60. [PubMed: 10891445]  [MGI Ref ID J:63087]

Kawasaki T; Dewerchin M; Lijnen HR; Vreys I; Vermylen J; Hoylaerts MF. 2001. Mouse carotid artery ligation induces platelet-leukocyte-dependent luminal fibrin, required for neointima development. Circ Res 88(2):159-66. [PubMed: 11157667]  [MGI Ref ID J:115383]

Koh TJ; Bryer SC; Pucci AM; Sisson TH. 2005. Mice deficient in plasminogen activator inhibitor-1 have improved skeletal muscle regeneration. Am J Physiol Cell Physiol 289(1):C217-23. [PubMed: 15716324]  [MGI Ref ID J:104684]

Lazar MH; Christensen PJ; Du M; Yu B; Subbotina NM; Hanson KE; Hansen JM; White ES; Simon RH; Sisson TH. 2004. Plasminogen activator inhibitor-1 impairs alveolar epithelial repair by binding to vitronectin. Am J Respir Cell Mol Biol 31(6):672-8. [PubMed: 15308506]  [MGI Ref ID J:104660]

Leonardsson G; Peng XR; Liu K; Nordstrom L; Carmeliet P; Mulligan R; Collen D; Ny T. 1995. Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators. Proc Natl Acad Sci U S A 92(26):12446-50. [PubMed: 8618918]  [MGI Ref ID J:31086]

Levi M; Moons L; Bouche A; Shapiro SD; Collen D; Carmeliet P. 2001. Deficiency of urokinase-type plasminogen activator-mediated plasmin generation impairs vascular remodeling during hypoxia-induced pulmonary hypertension in mice. Circulation 103(15):2014-20. [PubMed: 11306532]  [MGI Ref ID J:135010]

Li J; Ny A; Leonardsson G; Nandakumar KS; Holmdahl R; Ny T. 2005. The Plasminogen Activator/Plasmin System Is Essential for Development of the Joint Inflammatory Phase of Collagen Type II-Induced Arthritis. Am J Pathol 166(3):783-92. [PubMed: 15743790]  [MGI Ref ID J:96720]

Liu K; Wahlberg P; Hagglund AC; Ny T. 2003. Expression pattern and functional studies of matrix degrading proteases and their inhibitors in the mouse corpus luteum. Mol Cell Endocrinol 205(1-2):131-40. [PubMed: 12890575]  [MGI Ref ID J:126215]

Liu Z; Li N; Diaz LA; Shipley M; Senior RM; Werb Z. 2005. Synergy between a plasminogen cascade and MMP-9 in autoimmune disease. J Clin Invest 115(4):879-887. [PubMed: 15841177]  [MGI Ref ID J:97324]

Lluis F; Roma J; Suelves M; Parra M; Aniorte G; Gallardo E; Illa I; Rodriguez L; Hughes SM; Carmeliet P; Roig M; Munoz-Canoves P. 2001. Urokinase-dependent plasminogen activation is required for efficient skeletal muscle regeneration in vivo. Blood 97(6):1703-11. [PubMed: 11238111]  [MGI Ref ID J:68083]

Lund LR; Bjorn SF; Sternlicht MD; Nielsen BS; Solberg H; Usher PA; Osterby R; Christensen IJ; Stephens RW; Bugge TH; Dano K; Werb Z. 2000. Lactational competence and involution of the mouse mammary gland require plasminogen Development 127(20):4481-92. [PubMed: 11003846]  [MGI Ref ID J:64966]

Lund LR; Green KA; Stoop AA; Ploug M; Almholt K; Lilla J; Nielsen BS; Christensen IJ; Craik CS; Werb Z; Dano K; Romer J. 2006. Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice. EMBO J 25(12):2686-97. [PubMed: 16763560]  [MGI Ref ID J:119017]

Mahoney MG; Wang ZH; Stanley JR. 1999. Pemphigus vulgaris and pemphigus foliaceus antibodies are pathogenic in plasminogen activator knockout mice. J Invest Dermatol 113(1):22-5. [PubMed: 10417613]  [MGI Ref ID J:119605]

Matys T; Pawlak R; Strickland S. 2005. Tissue plasminogen activator in the bed nucleus of stria terminalis regulates acoustic startle. Neuroscience 135(3):715-22. [PubMed: 16125860]  [MGI Ref ID J:104429]

Minor KH; Seeds NW. 2008. Plasminogen activator induction facilitates recovery of respiratory function following spinal cord injury. Mol Cell Neurosci 37(1):143-52. [PubMed: 18042398]  [MGI Ref ID J:132690]

Morange PE; Bastelica D; Bonzi MF; Van Hoef B; Collen D; Juhan-Vague I; Lijnen HR. 2002. Influence of t-pA and u-PA on adipose tissue development in a murine model of diet-induced obesity. Thromb Haemost 87(2):306-10. [PubMed: 11858492]  [MGI Ref ID J:113728]

Nagai N; De Mol M; Lijnen HR; Carmeliet P; Collen D. 1999. Role of plasminogen system components in focal cerebral ischemic infarction: a gene targeting and gene transfer study in mice. Circulation 99(18):2440-4. [PubMed: 10318667]  [MGI Ref ID J:55243]

Nagai N; Okada K; Kawao N; Ishida C; Ueshima S; Collen D; Matsuo O. 2008. Urokinase-type plasminogen activator receptor (uPAR) augments brain damage in a murine model of ischemic stroke. Neurosci Lett 432(1):46-9. [PubMed: 18164548]  [MGI Ref ID J:141630]

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]

Nishiuma T; Sisson TH; Subbotina N; Simon RH. 2004. Localization of plasminogen activator activity within normal and injured lungs by in situ zymography. Am J Respir Cell Mol Biol 31(5):552-8. [PubMed: 15284078]  [MGI Ref ID J:103595]

Oh CW; Hoover-Plow J; Plow EF. 2003. The role of plasminogen in angiogenesis in vivo. J Thromb Haemost 1(8):1683-7. [PubMed: 12911578]  [MGI Ref ID J:128184]

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]

Piguet PF; Vesin C; Da Laperousaz C; Rochat A. 2000. Role of plasminogen activators and urokinase receptor in platelet kinetics. Hematol J 1(3):199-205. [PubMed: 11920190]  [MGI Ref ID J:103182]

Pinsky DJ; Liao H; Lawson CA; Yan SF; Chen J; Carmeliet P; Loskutoff DJ; Stern DM. 1998. Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition. J Clin Invest 102(5):919-28. [PubMed: 9727060]  [MGI Ref ID J:112025]

Ploplis VA; Tipton H; Menchen H; Castellino FJ. 2007. A urokinase-type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in ApcMin/+ mice. J Pathol 213(3):266-74. [PubMed: 17893885]  [MGI Ref ID J:126931]

Rakic JM; Lambert V; Munaut C; Bajou K; Peyrollier K; Alvarez-Gonzalez ML; Carmeliet P; Foidart JM; Noel A. 2003. Mice without uPA, tPA, or plasminogen genes are resistant to experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44(4):1732-9. [PubMed: 12657615]  [MGI Ref ID J:82604]

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]

Rijneveld AW; Levi M; Florquin S; Speelman P; Carmeliet P; van Der Poll T. 2002. Urokinase receptor is necessary for adequate host defense against pneumococcal pneumonia. J Immunol 168(7):3507-11. [PubMed: 11907112]  [MGI Ref ID J:75573]

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]

Schafer K; Konstantinides S; Riedel C; Thinnes T; Muller K; Dellas C; Hasenfuss G; Loskutoff DJ. 2002. Different mechanisms of increased luminal stenosis after arterial injury in mice deficient for urokinase- or tissue-type plasminogen activator. Circulation 106(14):1847-52. [PubMed: 12356640]  [MGI Ref ID J:103219]

Shapiro RL; Duquette JG; Nunes I; Roses DF; Harris MN; Wilson EL ; Rifkin DB. 1997. Urokinase-type plasminogen activator-deficient mice are predisposed to staphylococcal botryomycosis, pleuritis, and effacement of lymphoid follicles. Am J Pathol 150(1):359-69. [PubMed: 9006351]  [MGI Ref ID J:37695]

Shushakova N; Eden G; Dangers M; Zwirner J; Menne J; Gueler F; Luft FC; Haller H; Dumler I. 2005. The urokinase/urokinase receptor system mediates the IgG immune complex-induced inflammation in lung. J Immunol 175(6):4060-8. [PubMed: 16148155]  [MGI Ref ID J:116701]

Siconolfi LB; Seeds NW. 2001. Mice lacking tPA, uPA, or plasminogen genes showed delayed functional recovery after sciatic nerve crush. J Neurosci 21(12):4348-55. [PubMed: 11404420]  [MGI Ref ID J:123804]

Suelves M; Vidal B; Serrano AL; Tjwa M; Roma J; Lopez-Alemany R; Luttun A; de Lagran MM; Diaz-Ramos A; Jardi M; Roig M; Dierssen M; Dewerchin M; Carmeliet P; Munoz-Canoves P. 2007. uPA deficiency exacerbates muscular dystrophy in MDX mice. J Cell Biol 178(6):1039-51. [PubMed: 17785520]  [MGI Ref ID J:134802]

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]

Uhrin P; Schofer C; Zaujec J; Ryban L; Hilpert M; Weipoltshammer K; Jerabek I; Pirtzkall I; Furtmuller M; Dewerchin M; Binder BR; Geiger M. 2007. Male fertility and protein C inhibitor/plasminogen activator inhibitor-3 (PCI): localization of PCI in mouse testis and failure of single plasminogen activator knockout to restore spermatogenesis in PCI-deficient mice. Fertil Steril 88(4 Suppl):1049-57. [PubMed: 17434507]  [MGI Ref ID J:129635]

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]

Yamaguchi I; Lopez-Guisa JM; Cai X; Collins SJ; Okamura DM; Eddy AA. 2007. Endogenous urokinase lacks antifibrotic activity during progressive renal injury. Am J Physiol Renal Physiol 293(1):F12-9. [PubMed: 17356128]  [MGI Ref ID J:141660]

Yang YH; Carmeliet P; Hamilton JA. 2001. Tissue-type plasminogen activator deficiency exacerbates arthritis. J Immunol 167(2):1047-52. [PubMed: 11441114]  [MGI Ref ID J:120523]

Yepes M; Sandkvist M; Moore EG; Bugge TH; Strickland DK; Lawrence DA. 2003. Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. J Clin Invest 112(10):1533-40. [PubMed: 14617754]  [MGI Ref ID J:119309]

Yiou R; Delmas V; Carmeliet P; Gherardi RK; Barlovatz-Meimon G; Chopin DK; Abbou CC; Lefaucheur JP. 2001. The pathophysiology of pelvic floor disorders: evidence from a histomorphologic study of the perineum and a mouse model of rectal prolapse. J Anat 199(Pt 5):599-607. [PubMed: 11760891]  [MGI Ref ID J:73613]

de Giorgio-Miller A; Bottoms S; Laurent G; Carmeliet P; Herrick S. 2005. Fibrin-induced skin fibrosis in mice deficient in tissue plasminogen activator. Am J Pathol 167(3):721-32. [PubMed: 16127152]  [MGI Ref ID J:100676]

Health & husbandry

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Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. 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.

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	000651 BALB/cJ
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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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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.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.