JAX
Mouse Strain Datasheet - 002509
B6.129S2-Plautm1Mlg/J
Also Known As: uPA-
These Plau knock-out mice exhibit occasional rectal prolapse and fibrin deposition.
Donating Investigator
Dr. Peter Carmeliet, University of Leuven
Genetic overview
| Genetic Background | Generation |
|---|---|
|
C57BL/6 |
|
Plautm1Mlg
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | Plau | plasminogen activator, urokinase |
Research Applications
- Hematological Research
- Metabolism Research
- Neurobiology Research
Detailed Description
Homozygotes develop normally, have a normal life span, and are poor breeders. Pups often need fostering. 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.
Development
This targeted mutant was made in the laboratories of Dr. Richard Mulligan of the Whitehead Institute for Biomedical Sciences, Cambridge Massachusetts and of Dr. Peter Carmellet at the Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium. A targeting vector was used which resulted in the neomycin-resistant gene (neo) replacing all but 23 amino acids of the coding sequence. Targeting was done in 129S2/SvPas-derived D3 ES cells.
Control Suggestions
- Wild-type from the colony
- 000664 C57BL/6J
Additional Information
Selected References
- 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: 8133887MGI: J:17427
Plautm1Mlg
Allele Symbol: Plautm1Mlg
| Allele Name | targeted mutation 1, Richard C Mulligan |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | UPA-; u-PA-; uPA- |
| Gene Symbol and Name | Plau, plasminogen activator, urokinase |
| Gene Synonym(s) | ATF; BDPLT5; QPD; UPA; UPAM; URK; u-PA; uPA; urokinase-type plasminogen activator |
| Strain of Origin | 129S2/SvPas |
| Chromosome | 14 |
| 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. |
| Mutations Made By | Dr. Peter Carmeliet, University of Leuven |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
Genotype: Plautm1Mlg related
- Hematological Research
- Clotting Defects
- Metabolism Research
- Neurobiology Research
- Alzheimer's Disease
Mammalian Phenotype Terms by Genotype
Genotype: Plautm1Mlg/Plautm1Mlg
B6.129S2-Plautm1Mlg
mortality/aging
- premature death
- only 5 of 8 mice survive for a year (MGI Ref ID J:164542)
immune system phenotype
- chronic inflammation
- chronic inflammation is secondary to fibrin deposition (MGI Ref ID J:164542)
- increased inflammatory response
- liver inflammation
- the number of inflammatory foci is increased compared to in wild-type mice (MGI Ref ID J:164542)
- trachea inflammation
- all mice exhibit inflammation in the trachea (MGI Ref ID J:164542)
liver/biliary system phenotype
- decreased liver glycogen level
- (MGI Ref ID J:164542)
- liver fibrosis
- 2.5-fold more frequent in number compared with Plautm1.1Bug or Plaurtm1Jld homozygotes (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
- abnormal response to injury
- decreased liver glycogen level
- (MGI Ref ID J:164542)
respiratory system phenotype
- abnormal trachea morphology
- all mice exhibit inflammation in the trachea with basement membrane hyperplasia and desquamation of the tracheal epithelium unlike in wild-type mice (MGI Ref ID J:164542)
- trachea fibrosis
- mice exhibit fibrosis in the trachea unlike wild-type mice (MGI Ref ID J:164542)
- trachea inflammation
- all mice exhibit inflammation in the trachea (MGI Ref ID J:164542)
adipose tissue phenotype
- decreased total body fat amount
- (MGI Ref ID J:164542)
growth/size/body region phenotype
- cachexia
- some mice die before 1 year with a wasting syndrome (MGI Ref ID J:164542)
Genotype: Plautm1Mlg/Plautm1Mlg
either: B6.Cg-Plautm1Mlg or (involves: Black Swiss * C57BL/6)
homeostasis/metabolism phenotype
- reduced thrombolysis
- 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 (MGI Ref ID J:64220)
- in these mutants, impaired fibrinolysis can be rescued completely by providing urokinase exogenously (MGI Ref ID J:64220)
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Plautm1Mlg/Plautm1Mlg
B6.Cg-Plautm1Mlg
neoplasm
- abnormal tumor morphology
- 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 (MGI Ref ID J:65383)
- 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 (MGI Ref ID J:65383)
- ultrastructurally, fibrosarcoma tumor neovessels formed in mutant mice are larger and less mature than tumor vessels from wild-type mice (MGI Ref ID J:65383)
- decreased metastatic potential
- 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 (MGI Ref ID J:65383)
- notably, only mutants that survive for longer periods (2 months) after the injection develop these lesions, indicating a delay in metastasis (MGI Ref ID J:65383)
- decreased tumor growth/size
- 3 weeks after implantation of T241 fibrosarcoma cells, primary tumors from mutant mice are significantly smaller than tumors from wild-type mice (MGI Ref ID J:65383)
- 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 (MGI Ref ID J:65383)
cellular phenotype
- impaired macrophage chemotaxis
- in response to skeletal muscle degeneration, homozygotes display a 50% reduction in macrophage recruitment at the injury site 48 hours after glycerol-induced injury (MGI Ref ID J:68083)
digestive/alimentary phenotype
- abnormal perineum morphology
- in males with rectal prolapse, the perineal region is swollen on both sides of the evaginated rectal mucosa (MGI Ref ID J:73613)
- abnormal rectum morphology
- in males with rectal prolapse, the rectal mucosa is exteriorized and evaginated (MGI Ref ID J:73613)
- rectal prolapse
endocrine/exocrine gland phenotype
- herniated seminal vesicle
- 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 (MGI Ref ID J:73613)
- this hernia results in chronic stretching and thinning of the ISC, BC, and levator ani (LA) pelvic floor muscles (MGI Ref ID J:73613)
immune system phenotype
- abnormal acute phase protein level
- at 9 days after glycerol-induced injury of skeletal muscles, homozygotes exhibit abundant fibrin deposits in degenerating muscle fibers (MGI Ref ID J:68083)
- abnormal cytokine level
- in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in TNF levels in the synovium relative to wild-type (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 (MGI Ref ID J:75303)
- decreased T cell proliferation
- 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 (MGI Ref ID J:75303)
- decreased inflammatory response
- 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 (MGI Ref ID J:68083)
- decreased susceptibility to induced arthritis
- in a model of collagen-induced arthritis, homozygotes develop a significantly milder disease than wild-type mice, with little inflammation and joint destruction (MGI Ref ID J:75303)
- 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 (MGI Ref ID J:75303)
- surprisingly, the joints of arthritic homozygotes display minimal fibrin(ogen) deposition relative to wild-type (MGI Ref ID J:75303)
- impaired macrophage chemotaxis
- in response to skeletal muscle degeneration, homozygotes display a 50% reduction in macrophage recruitment at the injury site 48 hours after glycerol-induced injury (MGI Ref ID J:68083)
muscle phenotype
- impaired skeletal muscle regeneration
- at 5 days after injury, skeletal muscles from mutant mice appear edematous; in contrast to wild-type, no uninucleated, small myofibers are yet formed (MGI Ref ID J:68083)
- at 7 days after injury, most injured skeletal muscles appear necrotic and show extensive fibrosis (MGI Ref ID J:68083)
- 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 (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 (MGI Ref ID J:68083)
- 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 (MGI Ref ID J:68083)
- myopathy
reproductive system phenotype
- abnormal perineum morphology
- in males with rectal prolapse, the perineal region is swollen on both sides of the evaginated rectal mucosa (MGI Ref ID J:73613)
- herniated seminal vesicle
- 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 (MGI Ref ID J:73613)
- this hernia results in chronic stretching and thinning of the ISC, BC, and levator ani (LA) pelvic floor muscles (MGI Ref ID J:73613)
skeleton phenotype
- decreased susceptibility to induced arthritis
- in a model of collagen-induced arthritis, homozygotes develop a significantly milder disease than wild-type mice, with little inflammation and joint destruction (MGI Ref ID J:75303)
- 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 (MGI Ref ID J:75303)
- surprisingly, the joints of arthritic homozygotes display minimal fibrin(ogen) deposition relative to wild-type (MGI Ref ID J:75303)
homeostasis/metabolism phenotype
- abnormal acute phase protein level
- at 9 days after glycerol-induced injury of skeletal muscles, homozygotes exhibit abundant fibrin deposits in degenerating muscle fibers (MGI Ref ID J:68083)
- abnormal cytokine level
- in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant reduction in TNF levels in the synovium relative to wild-type (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 (MGI Ref ID J:75303)
hematopoietic system phenotype
- decreased T cell proliferation
- 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 (MGI Ref ID J:75303)
- impaired macrophage chemotaxis
- in response to skeletal muscle degeneration, homozygotes display a 50% reduction in macrophage recruitment at the injury site 48 hours after glycerol-induced injury (MGI Ref ID J:68083)
Genotype: Plautm1Mlg/Plautm1Mlg
involves: 129S2/SvPas * C57BL/6
mortality/aging
- mortality/aging
- homozygotes display a normal lifespan relative to wild-type mice (MGI Ref ID J:17427)
respiratory system phenotype
- pulmonary interstitial fibrosis
- 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 (MGI Ref ID J:63134)
- 62% of bleomycin-treated homozygotes die as early as ~7 days after treatment, possibly as a result of extensive fibrosis (MGI Ref ID J:63134)
- 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 (MGI Ref ID J:63134)
vision/eye phenotype
- abnormal eyelid morphology
- at ~26 weeks of age, 5% homozygotes display severe non-healing ulcerations at the eyelids (MGI Ref ID J:17427)
- decreased susceptibility to induced choroidal neovascularization
- 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 (MGI Ref ID J:82604)
- resistance to CNV is associated with excessive fibrinogen-fibrin deposition at the site of choroidal trauma and in retinal vessels (MGI Ref ID J:82604)
nervous system phenotype
- nervous system phenotype
- Abeta40 and 42 levels are not increased in mutant brains relative to controls (MGI Ref ID J:104962)
- 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 (MGI Ref ID J:55243)
homeostasis/metabolism phenotype
- abnormal acute phase protein level
- 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 (MGI Ref ID J:82604)
- bleomycin-treated homozygotes exhibit extensive areas of fibrin(ogen) deposition in the lung interstitium which are associated with areas of fibrosis (MGI Ref ID J:63134)
- abnormal circulating protein level
- 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 (MGI Ref ID J:104962)
- abnormal thrombosis
- 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 (MGI Ref ID J:17427)
- 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)s per tissue section versus only 15% in wild-type) (MGI Ref ID J:17427)
craniofacial phenotype
- abnormal outer ear morphology
- at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the ear tag and the face (MGI Ref ID J:17427)
cellular phenotype
- impaired macrophage chemotaxis
- 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 (MGI Ref ID J:63134)
- 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 (MGI Ref ID J:63134)
growth/size/body region phenotype
- abnormal outer ear morphology
- at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the ear tag and the face (MGI Ref ID J:17427)
- growth/size/body region phenotype
- at 5 weeks of age, homozygotes exhibit a normal body weight relative to wild-type mice (MGI Ref ID J:17427)
cardiovascular system phenotype
- cardiac interstitial fibrosis
- 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 (MGI Ref ID J:95236)
- decreased susceptibility to induced choroidal neovascularization
- 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 (MGI Ref ID J:82604)
- resistance to CNV is associated with excessive fibrinogen-fibrin deposition at the site of choroidal trauma and in retinal vessels (MGI Ref ID J:82604)
- heart left ventricle hypertrophy
- after transverse aortic banding (TAB), i.e. acute pressure overload, homozygotes remain significantly protected against LV hypertrophy for at least 7 weeks (MGI Ref ID J:95236)
- at 7 weeks after TAB, LV systolic dysfunction and dilatation are only marginally detectable without signs of pulmonary edema (MGI Ref ID J:95236)
- 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) (MGI Ref ID J:95236)
- increased ventricle muscle contractility
- at 7 weeks after TAB, homozygotes exhibit increased LV contractility, indicating normal fractional shortening with no cardiac failure or pulmonary congestion (MGI Ref ID J:95236)
digestive/alimentary phenotype
- rectal prolapse
- at ~22 weeks of age, 9% of homozygotes display rectal prolapse of a non-infectious origin (MGI Ref ID J:17427)
hearing/vestibular/ear phenotype
- abnormal outer ear morphology
- at ~26 weeks of age, 5% of homozygotes display severe non-healing ulcerations at the ears around the ear tag and the face (MGI Ref ID J:17427)
hematopoietic system phenotype
- abnormal macrophage physiology
- 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 unaffectedmains unaffected (MGI Ref ID J:17427)
- abnormal neutrophil physiology
- 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-typelative to wild-type (MGI Ref ID J:75573)
- in contrast, mutant neutrophils show normal agonist-stimulated release of specific granules relative to wild-type neutrophils (MGI Ref ID J:91980)
- 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 (MGI Ref ID J:91980)
- 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 reverses the defect in superoxide generation (MGI Ref ID J:91980)
- hematopoietic system phenotype
- homozygotes exhibit normal spontaneous lysis of a 125I-fibrin-labeled pulmonary plasma clot relative to wild-type (MGI Ref ID J:17427)
- impaired granulocyte bactericidal activity
- 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 (MGI Ref ID J:91980)
- impaired macrophage chemotaxis
- 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 (MGI Ref ID J:63134)
- 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 (MGI Ref ID J:63134)
- impaired neutrophil phagocytosis
- 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 (MGI Ref ID J:91980)
- increased lymphocyte cell number
- 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 (MGI Ref ID J:63134)
immune system phenotype
- abnormal acute phase protein level
- 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 (MGI Ref ID J:82604)
- bleomycin-treated homozygotes exhibit extensive areas of fibrin(ogen) deposition in the lung interstitium which are associated with areas of fibrosis (MGI Ref ID J:63134)
- abnormal cell-mediated immunity
- homozygotes fail to generate a type 1 immune response in the lung during pulmonary fungal infection with C. neoformans (MGI Ref ID J:95638)
- homozygotes fail to generate a type 2 immune response following schistosomal antigen challenge (MGI Ref ID J:87817)
- 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 cytokineine (MGI Ref ID J:95638)
- 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 eosinophilse deficient in eosinophils (MGI Ref ID J:87817)
- abnormal macrophage physiology
- 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 unaffectedmains unaffected (MGI Ref ID J:17427)
- abnormal neutrophil physiology
- 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-typelative to wild-type (MGI Ref ID J:75573)
- in contrast, mutant neutrophils show normal agonist-stimulated release of specific granules relative to wild-type neutrophils (MGI Ref ID J:91980)
- 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 (MGI Ref ID J:91980)
- 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 reverses the defect in superoxide generation (MGI Ref ID J:91980)
- impaired granulocyte bactericidal activity
- 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 (MGI Ref ID J:91980)
- impaired macrophage chemotaxis
- 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 (MGI Ref ID J:63134)
- 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 (MGI Ref ID J:63134)
- impaired neutrophil phagocytosis
- 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 (MGI Ref ID J:91980)
- increased lymphocyte cell number
- 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 (MGI Ref ID J:63134)
- increased susceptibility to fungal infection
- 21 days after inoculation with Cryptococcus neoformans, homozygotes contain significantly higher lung CFUs than wild-type mice (MGI Ref ID J:95637)
- 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 (MGI Ref ID J:95637)
- increased susceptibility to parasitic infection
- when primed homozygotes are challenged with schistosomal egg antigen (SEA) they exhibit a severe immune defect in response to this T2-eliciting antigen (MGI Ref ID J:87817)
muscle phenotype
- increased ventricle muscle contractility
- at 7 weeks after TAB, homozygotes exhibit increased LV contractility, indicating normal fractional shortening with no cardiac failure or pulmonary congestion (MGI Ref ID J:95236)
reproductive system phenotype
- reproductive system phenotype
- homozygotes display normal litter size and frequency of litters relative to wild-type mice (MGI Ref ID J:17427)
References
- 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: 8133887MGI: 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: 8609247MGI: J:31253
Additional - Plautm1Mlg 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: 12759445MGI: J:131136
- Almholt K; Lund LR; Rygaard J; Nielsen BS; Dano K; Romer J; Johnsen M. 2005. Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice. Int J Cancer 113(4):525-32. PubMed: 15472905MGI: J:94645
- Bajou K; Herkenne S; Thijssen VL; D'Amico S; Nguyen NQ; Bouche A; Tabruyn S; Srahna M; Carabin JY; Nivelles O; Paques C; Cornelissen I; Lion M; Noel A; Gils A; Vinckier S; Declerck PJ; Griffioen AW; Dewerchin M; Martial JA; Carmeliet P; Struman I. 2014. PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin. Nat Med 20(7):741-7. PubMed: 24929950MGI: J:227609
- 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: 10961882MGI: 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: 11025665MGI: 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: 11238040MGI: J:114282
- Bhandary YP; Shetty SK; Marudamuthu AS; Ji HL; Neuenschwander PF; Boggaram V; Morris GF; Fu J; Idell S; Shetty S. 2013. Regulation of Lung Injury and Fibrosis by p53-Mediated Changes in Urokinase and Plasminogen Activator Inhibitor-1. Am J Pathol 183(1):131-43. PubMed: 23665346MGI: J:197439
- 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: 18178858MGI: 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: 9425170MGI: 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: 9351457MGI: 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: 9398846MGI: J:44387
- Chen Z; Zhao R; Zhao M; Liang X; Bhattarai D; Dhiman R; Shetty S; Idell S; Ji HL. 2014. Regulation of epithelial sodium channels in urokinase plasminogen activator deficiency. Am J Physiol Lung Cell Mol Physiol 307(8):L609-17. PubMed: 25172911MGI: J:222200
- Cho E; Lee KJ; Seo JW; Byun CJ; Chung SJ; Suh DC; Carmeliet P; Koh JY; Kim JS; Lee JY. 2012. Neuroprotection by urokinase plasminogen activator in the hippocampus. Neurobiol Dis 46(1):215-24. PubMed: 22293605MGI: J:182295
- 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: 10487767MGI: J:57461
- 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: 20466854MGI: J:164542
- 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: 11891190MGI: J:75303
- Crosswhite PL; Podsiadlowska JJ; Curtis CD; Gao S; Xia L; Srinivasan RS; Griffin CT. 2016. CHD4-regulated plasmin activation impacts lymphovenous hemostasis and hepatic vascular integrity. J Clin Invest 126(6):2254-66. PubMed: 27140400MGI: J:237076
- 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: 12854826MGI: 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: 12692088MGI: 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: 12600880MGI: J:115512
- Devy L; Blacher S; Grignet-Debrus C; Bajou K; Masson V; Gerard RD; Gils A; Carmeliet G; Carmeliet P; Declerck PJ; Noel A; Foidart JM. 2002. The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent. FASEB J 16(2):147-54. PubMed: 11818362MGI: J:74281
- 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: 17652428MGI: J:145128
- 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: 15615772MGI: J:104962
- Fleetwood AJ; Achuthan A; Schultz H; Nansen A; Almholt K; Usher P; Hamilton JA. 2014. Urokinase plasminogen activator is a central regulator of macrophage three-dimensional invasion, matrix degradation, and adhesion. J Immunol 192(8):3540-7. PubMed: 24616477MGI: J:210232
- 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: 18606671MGI: J:137466
- Guo Y; Li J; Hagstrom E; Ny T. 2011. Beneficial and detrimental effects of plasmin(ogen) during infection and sepsis in mice. PLoS One 6(9):e24774. PubMed: 21931850MGI: J:177689
- 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: 11059781MGI: 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: 15240745MGI: 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: 8621764MGI: 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: 10072260MGI: 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: 11777975MGI: 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: 14688127MGI: 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: 10903758MGI: 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: 15631996MGI: 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: 10502816MGI: 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: 16880329MGI: 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: 18279442MGI: J:133582
- Hijazi N; Abu Fanne R; Abramovitch R; Yarovoi S; Higazi M; Abdeen S; Basheer M; Maraga E; Cines DB; Higazi AA. 2015. Endogenous plasminogen activators mediate progressive intracerebral hemorrhage after traumatic brain injury in mice. Blood 125(16):2558-67. PubMed: 25673638MGI: J:222043
- 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: 19461880MGI: J:162185
- Ingram KG; Curtis CD; Silasi-Mansat R; Lupu F; Griffin CT. 2013. The NuRD chromatin-remodeling enzyme CHD4 promotes embryonic vascular integrity by transcriptionally regulating extracellular matrix proteolysis. PLoS Genet 9(12):e1004031. PubMed: 24348274MGI: J:207517
- Jogi A; Rono B; Lund IK; Nielsen BS; Ploug M; Hoyer-Hansen G; Romer J; Lund LR. 2010. Neutralisation of uPA with a monoclonal antibody reduces plasmin formation and delays skin wound healing in tPA-deficient mice. PLoS One 5(9):e12746. PubMed: 20856796MGI: J:165126
- Juncker-Jensen A; Lund LR. 2011. Phenotypic overlap between MMP-13 and the plasminogen activation system during wound healing in mice. PLoS One 6(2):e16954. PubMed: 21326869MGI: J:170892
- Kawao N; Tamura Y; Horiuchi Y; Okumoto K; Yano M; Okada K; Matsuo O; Kaji H. 2015. The Tissue Fibrinolytic System Contributes to the Induction of Macrophage Function and CCL3 during Bone Repair in Mice. PLoS One 10(4):e0123982. PubMed: 25893677MGI: J:233478
- Kawao N; Tamura Y; Okumoto K; Yano M; Okada K; Matsuo O; Kaji H. 2014. Tissue-type plasminogen activator deficiency delays bone repair: roles of osteoblastic proliferation and vascular endothelial growth factor. Am J Physiol Endocrinol Metab 307(3):E278-88. PubMed: 24918201MGI: J:215316
- 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: 10891445MGI: 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: 11157667MGI: 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: 15716324MGI: J:104684
- Kremen M; Krishnan R; Emery I; Hu JH; Slezicki KI; Wu A; Qian K; Du L; Plawman A; Stempien-Otero A; Dichek DA. 2008. Plasminogen mediates the atherogenic effects of macrophage-expressed urokinase and accelerates atherosclerosis in apoE-knockout mice. Proc Natl Acad Sci U S A 105(44):17109-14. PubMed: 18957535MGI: J:144061
- Lahtinen L; Ndode-Ekane XE; Barinka F; Akamine Y; Esmaeili MH; Rantala J; Pitkanen A. 2010. Urokinase-type plasminogen activator regulates neurodegeneration and neurogenesis but not vascular changes in the mouse hippocampus after status epilepticus. Neurobiol Dis 37(3):692-703. PubMed: 20026272MGI: J:158409
- 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: 15308506MGI: 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: 8618918MGI: 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: 11306532MGI: 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: 15743790MGI: 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: 12890575MGI: 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: 15841177MGI: 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: 11238111MGI: J:68083
- 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: 21802414MGI: J:176606
- 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: 11003846MGI: 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: 16763560MGI: 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: 10417613MGI: J:119605
- Marudamuthu AS; Bhandary YP; Shetty SK; Fu J; Sathish V; Prakash Y; Shetty S. 2015. Role of the Urokinase-Fibrinolytic System in Epithelial-Mesenchymal Transition during Lung Injury. Am J Pathol 185(1):55-68. PubMed: 25447049MGI: J:216959
- 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: 16125860MGI: J:104429
- Mazzieri R; Pietrogrande G; Gerasi L; Gandelli A; Colombo P; Moi D; Brombin C; Ambrosi A; Danese S; Mignatti P; Blasi F; D'Alessio S. 2015. Urokinase Receptor Promotes Skin Tumor Formation by Preventing Epithelial Cell Activation of Notch1. Cancer Res 75(22):4895-909. PubMed: 26527290MGI: J:226757
- Merino P; Diaz A; Jeanneret V; Wu F; Torre E; Cheng L; Yepes M. 2017. Urokinase-type Plasminogen Activator (uPA) Binding to the uPA Receptor (uPAR) Promotes Axonal Regeneration in the Central Nervous System. J Biol Chem 292(7):2741-2753. PubMed: 27986809MGI: J:240802
- 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: 18042398MGI: 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: 11858492MGI: J:113728
- Motley MP; Madsen DH; Jurgensen HJ; Spencer DE; Szabo R; Holmbeck K; Flick MJ; Lawrence DA; Castellino FJ; Weigert R; Bugge TH. 2016. A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo. Blood 127(9):1085-96. PubMed: 26647393MGI: J:232502
- 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: 10318667MGI: 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: 18164548MGI: 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: 12171938MGI: 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: 20097831MGI: J:179956
- 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: 15284078MGI: 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: 12911578MGI: 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: 10858190MGI: 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: 11920190MGI: 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: 9727060MGI: 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: 17893885MGI: J:126931
- Prager GW; Mihaly J; Brunner PM; Koshelnick Y; Hoyer-Hansen G; Binder BR. 2009. Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein. Blood 113(6):1383-90. PubMed: 18948573MGI: J:145580
- 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: 12657615MGI: J:82604
- Reichel CA; Uhl B; Lerchenberger M; Puhr-Westerheide D; Rehberg M; Liebl J; Khandoga A; Schmalix W; Zahler S; Deindl E; Lorenzl S; Declerck PJ; Kanse S; Krombach F. 2011. Urokinase-type plasminogen activator promotes paracellular transmigration of neutrophils via Mac-1, but independently of urokinase-type plasminogen activator receptor. Circulation 124(17):1848-59. PubMed: 21969013MGI: J:189465
- 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: 17114493MGI: 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: 11907112MGI: J:75573
- Sanderson-Smith ML; Zhang Y; Ly D; Donahue D; Hollands A; Nizet V; Ranson M; Ploplis VA; Walker MJ; Castellino FJ. 2013. A key role for the urokinase plasminogen activator (uPA) in invasive Group A streptococcal infection. PLoS Pathog 9(7):e1003469. PubMed: 23853591MGI: J:213368
- 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: 12875972MGI: 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: 12356640MGI: J:103219
- Shanmukhappa K; Matte U; Degen JL; Bezerra JA. 2009. Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repair. J Biol Chem 284(19):12917-23. PubMed: 19286661MGI: J:149628
- 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: 9006351MGI: J:37695
- Shen Y; Guo Y; Du C; Wilczynska M; Hellstrom S; Ny T. 2012. Mice deficient in urokinase-type plasminogen activator have delayed healing of tympanic membrane perforations. PLoS One 7(12):e51303. PubMed: 23236466MGI: J:195678
- 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: 16148155MGI: 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: 11404420MGI: J:123804
- Sisson TH; Nguyen MH; Yu B; Novak ML; Simon RH; Koh TJ. 2009. Urokinase-type plasminogen activator increases hepatocyte growth factor activity required for skeletal muscle regeneration. Blood 114(24):5052-61. PubMed: 19812386MGI: J:154983
- 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: 17785520MGI: J:134802
- Sugioka K; Kodama A; Yoshida K; Okada K; Mishima H; Aomatsu K; Matsuo O; Shimomura Y. 2014. The roles of urokinase-type plasminogen activator in leukocyte infiltration and inflammatory responses in mice corneas treated with lipopolysaccharide. Invest Ophthalmol Vis Sci 55(8):5338-50. PubMed: 25061113MGI: J:230111
- Sulniute R; Lindh T; Wilczynska M; Li J; Ny T. 2011. Plasmin is essential in preventing periodontitis in mice. Am J Pathol 179(2):819-28. PubMed: 21704601MGI: J:174401
- 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: 10880388MGI: J:63134
- Teesalu T; Blasi F; Talarico D. 1996. Embryo implantation in mouse: fetomaternal coordination in the pattern of expression of uPA, uPAR, PAI-1 and alpha 2MR/LRP genes. Mech Dev 56(1-2):103-16. PubMed: 8798151MGI: J:33753
- 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: 21868698MGI: J:191466
- 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: 17434507MGI: J:129635
- Van Den Broeck T; Stevenaert F; Taveirne S; Debacker V; Vangestel C; Vandekerckhove B; Taghon T; Matthys P; Plum J; Held W; Dewerchin M; Yokoyama WM; Leclercq G. 2008. Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator. Blood 112(13):5046-51. PubMed: 18784372MGI: J:143621
- 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: 18084301MGI: J:130835
- Weiler-Guettler H; Christie PD; Beeler DL; Healy AM; Hancock WW; Rayburn H; Edelberg JM; Rosenberg RD. 1998. A targeted point mutation in thrombomodulin generates viable mice with a prethrombotic state. J Clin Invest 101(9):1983-91. PubMed: 9576763MGI: J:47676
- Wu F; Catano M; Echeverry R; Torre E; Haile WB; An J; Chen C; Cheng L; Nicholson A; Tong FC; Park J; Yepes M. 2014. Urokinase-type plasminogen activator promotes dendritic spine recovery and improves neurological outcome following ischemic stroke. J Neurosci 34(43):14219-32. PubMed: 25339736MGI: J:217155
- 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: 17356128MGI: J:141660
- Yang YH; Carmeliet P; Hamilton JA. 2001. Tissue-type plasminogen activator deficiency exacerbates arthritis. J Immunol 167(2):1047-52. PubMed: 11441114MGI: 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: 14617754MGI: 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: 11760891MGI: 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: 16127152MGI: J:100676