Description

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. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S2 via D3 ES cell line Generation N8F12 (18-DEC-08)   Donating Investigator Peter Carmeliet,   University of Leuven

Appearance
black
Related Genotype: a/a

Description
Homozygotes develop normally, are fertile and have a normal life span. There are no histological abnormalities. Pulmonary clot lysis is 21% that of normal wildtype siblings. Endotoxin induced venous thrombosis is increased over that seen in normal wildtype siblings. Fibrin dissolution by PLAT-deficient macrophages is unaffected.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Plat^tm1Mlg allele

002327	C.129S2-Plattm1Mlg/J
002326	STOCK Plattm1Mlg/J

View Strains carrying   Plat^tm1Mlg     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Plat^tm1Mlg/Plat^tm1Mlg

        B6.Cg-Plat^tm1Mlg

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:89431)
  • homozygotes show normal footshock sensitivity thresholds relative to wild-type mice
• abnormal active avoidance behavior (MGI Ref ID J:89431)
  • homozygotes display poor active avoidance behavior relative to wild-type mice
• abnormal contextual conditioning (MGI Ref ID J:89431)
  • homozygotes display poor contextual fear conditioning behavior relative to wild-type mice, indicating impaired hippocampal function
• abnormal cued conditioning behavior (MGI Ref ID J:89431)
  • homozygotes display enhanced cue fear conditioning behavior relative to wild-type mice
• abnormal motor learning (MGI Ref ID J:84875)
  • relative to wild-type, mutant mice exhibit a 28% reduction in both the rate and extent of learning a complex motor paradigm of irregular peg running, indicating impaired cerebellar motor learning
• abnormal response to addictive substance (MGI Ref ID J:88913)
  • homozygotes show no significant differences in the antinociceptive effect of morphine or development of its tolerance relative to wild-type mice
  • notably, homozygotes display a significant reduction in morphine-induced conditioned place preference and hyperlocomotion relative to wild-type
  • the defect of morphine-induced hyperlocomotion is reversed by exogenous administration of tPA or plasmin into the nucleus accumbens (Nacc)
• decreased anxiety-related response (MGI Ref ID J:81694)
  • after up to 3 weeks of daily restraint, homozygotes exhibit absence of stress-induced anxiety in the elevated-plus maze; in wild-type, acute stress resuls in a decrease in open arm entries, with 21 days of daily restraint leading to some habituation
  • in response to a low or middle dose of corticotropin-releasing factor (CRF), homozygotes exhibit reduced anxiety (lower number of open arm entries) in the elevated plus-maze, with an increased number of head dips (increased exploration) relative to wild-type
  • in response to a high dose of CRF, homozygotes fail to explore the open arms but display a similar number of closed arms entries relative to wild-type mice, indicating normal locomotor activity
• decreased exploration in new environment (MGI Ref ID J:89431)
  • homozygotes display no habitation of object exploration relative to wild-type mice
  • homozygotes show no reactivity to spatial change (measured as renewed exploration of displaced objects) relative to wild-type mice
• decreased vertical activity (MGI Ref ID J:89431)
  • in an empty open field, homozygotes show normal horizontal activity but significantly reduced rearing activity 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 increase in interleukin-1beta levels in the synovium relative to wild-type
  • in a model of collagen-induced arthritis, ankle joint washouts from arthritic homozygotes exhibit a significant increase in TNF levels relative to wild-type
• abnormal fibrinogen physiology (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, severely affected joints from homozygotes display diffuse fibrin(ogen) deposition relative to wild-type
  • within arthritic joints, higher fibrin levels appear to correlate with increased disease severity
• increased circulating corticosterone level (MGI Ref ID J:94733)
  • homozygotes show normal up-regulation of corticosterone in response to CRF but sustain elevation of corticosterone level during recovery
  • after a 30-min restraint stress, homozygotes exhibit a 30% increase in corticosterone levels relative to wil-type
  • unlike wild-type mice, corticosterone levels in mutant mice do not return to pre-stress levels after a 90-min recovery period
• 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
• immune system phenotype
• abnormal cytokine level (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, arthritic homozygotes exhibit a significant increase in interleukin-1beta levels in the synovium relative to wild-type
  • in a model of collagen-induced arthritis, ankle joint washouts from arthritic homozygotes exhibit a significant increase in TNF levels relative to wild-type
• abnormal fibrinogen physiology (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, severely affected joints from homozygotes display diffuse fibrin(ogen) deposition relative to wild-type
  • within arthritic joints, higher fibrin levels appear to correlate with increased disease severity
• arthritis (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, homozygotes develop a significantly more severe arthritis than wild-type mice
  • 95% of mutant mice develop arthritis compared with 68% of wild-type mice; no difference in the day of disease onset is observed
  • severely affected joints from arthritic homozygotes exhibit higher cartilage damage and bone erosions than wild-type mice
• chronic joint inflammation (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, homozygotes develop significant joint inflammation and joint destruction relative to wild-type mice
  • severely affected joints from arthritic homozygotes exhibit massive cell infiltration and higher proteoglycan depletion than wild-type mice
• muscle phenotype
• *normal* muscle phenotype (MGI Ref ID J:68083)
  • in response to glycerol-induced injury, homozygotes exhibit normal skeletal muscle regeneration after 5 days; regeneration is complete after 9 days
  • at 7 days after injury, most injured fibers regenerate into groups of centrally nucleated myotubes, indicating advanced regeneration; only few necrotic fibers are observed
  • at 20 days after injury, virtually no signs of muscle injury are detected, except for centrally located myonuclei inside the regenerated fibers
• skeleton phenotype
• arthritis (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, homozygotes develop a significantly more severe arthritis than wild-type mice
  • 95% of mutant mice develop arthritis compared with 68% of wild-type mice; no difference in the day of disease onset is observed
  • severely affected joints from arthritic homozygotes exhibit higher cartilage damage and bone erosions than wild-type mice
• chronic joint inflammation (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, homozygotes develop significant joint inflammation and joint destruction relative to wild-type mice
  • severely affected joints from arthritic homozygotes exhibit massive cell infiltration and higher proteoglycan depletion than wild-type mice
• joint swelling (MGI Ref ID J:75303)
  • in a model of collagen-induced arthritis, 60% of mutant mice have 3 or 4 affected limbs compared with only 18% of wild-type mice
  • in arthritic mutants, 45% of affected individual limbs display severe swelling and/or rigidity compared with only 19% from wild-type
  • there are no differences in the degree of swelling (i.e. paw thickness) between limbs from mutant and wild-type mice with the same clinical score
• nervous system phenotype
• absent long term depression (MGI Ref ID J:89431)
  • in response to tetanic stimulation of corticostriatal fibers, homozygotes display absence of LTD in a significant portion of striatal neurons
• decreased dopamine level (MGI Ref ID J:88913)
  • homozygotes exhibit loss of morphine-induced dopamine release in the nucleus accumbens (Nacc)
  • the defect of morphine-induced dopamine release is reversed by exogenous administration of tPA or plasmin into the Nacc but not into the ventral tegmental area (VTA)
• impaired synaptic plasticity (MGI Ref ID J:81694)
  • after restraint, homozygotes show reduced neuronal remodeling in the medial amygdala, with absence of stress-induced ERK1/2 phosphorylation at all time points tested
  • in response to CRF, homozygotes exhibit attenuated expression of Fos (an indicator of neuronal activation) in the central and medial amygdala but show normal Fos responses in paraventricular nuclei
• reduced long term potentiation (MGI Ref ID J:89431)
  • in response to tetanic stimulation, hippocampal CA1 slices from mutant mice show a significant reduction in the late phase of LTP relative to wild-type
  • notably, a slight but significant reduction of the early phase of hippocampal LTP is also observed

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

Plat^tm1Mlg/Plat^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
• cardiovascular system phenotype
• cardiac interstitial fibrosis (MGI Ref ID J:95236)
  • in response to pressure overload, wild-type and mutant mice display similar signs of maladaptation (i.e. myolysis, myocardial fibrosis and increased intercapillary distance)
• decreased ventricle muscle contractility (MGI Ref ID J:95236)
  • at 7 weeks after TAB, wild-type and mutant mice exhibit a similar degree of LV dilatation, obvious signs of LV systolic dysfunction, and pump failure
  • at 7 weeks after TAB, impaired fractional shortening and abnormal cardiac pump result in respiratory distress due to pulmonary congestion
• 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
• intracerebral hemorrhage (MGI Ref ID J:89052)
  • in a photothrombotic model of middle cerebral artery occlusion (MCAO), delayed heparin administration increases cerebral hemorrhage associated with ischemia in wild-type but NOT in mutant mice
  • in this MCAO model, heparin administration induces tPA activity and mRNA expression in microglial cells, and enhances MMP9 expression and proteolytic activation in the ischemic brains of wild-type but NOT of mutant mice
• left ventricle hypertrophy (MGI Ref ID J:95236)
  • at 2 weeks after transverse aortic banding (TAB) i.e. acute pressure overload, homozygotes and wild-type mice exhibit a significant LV hypertrophy which persists for up to 7 weeks
  • similar to wild-type mice, homozygotes display a ~35% increase in LV/body weight ratio and a ~40% increase in the LV cardiomyocyte size
• lung hemorrhage (MGI Ref ID J:63134)
  • 11 days after bleomycin treatment, mutant lungs show areas of fibrosis surrounded by areas of extensive intra-alveolar hemorrhage
  • hemorrhagic areas contain numerous hemosiderin-laden macrophages, indicating chronic pulmonary hemorrhage
• 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
  • no macroscopic or histologic abnormalities are observed up to 14 months of age
• hematopoietic system phenotype
• increased macrophage cell number (MGI Ref ID J:63134)
  • bleomycin-treated homozygotes display a delayed, but significant, increase in macrophage levels reaching wild-type levels at 9 days post-drug treatment
• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:17427)
  • homozygotes exhibit normal matrix degradation and invasion into the peritoneal cavity by thioglycollate-stimulated macrophages
• abnormal fibrinogen physiology (MGI Ref ID J:82604)
  • 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
  • after bleomycin treatment, homozygotes exhibit areas of fibrin(ogen) deposits, especially in the vasculature of the lung, where fibrin thrombi are observed
• increased macrophage cell number (MGI Ref ID J:63134)
  • bleomycin-treated homozygotes display a delayed, but significant, increase in macrophage levels reaching wild-type levels at 9 days post-drug treatment
• muscle phenotype
• decreased ventricle muscle contractility (MGI Ref ID J:95236)
  • at 7 weeks after TAB, wild-type and mutant mice exhibit a similar degree of LV dilatation, obvious signs of LV systolic dysfunction, and pump failure
  • at 7 weeks after TAB, impaired fractional shortening and abnormal cardiac pump result in respiratory distress due to 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
• lung hemorrhage (MGI Ref ID J:63134)
  • 11 days after bleomycin treatment, mutant lungs show areas of fibrosis surrounded by areas of extensive intra-alveolar hemorrhage
  • hemorrhagic areas contain numerous hemosiderin-laden macrophages, indicating chronic pulmonary hemorrhage
• pulmonary interstitial fibrosis (MGI Ref ID J:63134)
  • bleomycin-treated homozygotes exhibit an enhanced increase in lung hydroxyproline (collagen) content relative to bleomycin-treated wild-type mice
  • histological analysis after lung injury indicates extensive interstitial fibrosis in mutant mice relative to wild-type
  • notably, homozygotes survive only 11 days post-drug treatment
  • 75% of bleomycin-treated homozygotes die as early as 7 days after treatment, as a result of hemorrhage and extensive fibrotic lesions
• vision/eye phenotype
• abnormal retinal apoptosis (MGI Ref ID J:93533)
  • at 12 and 24 h after intravitreal injection of low-dose (30 nmol/mouse) NMDA, homozygotes contain significantly less retinal apoptotic neurons in the ganglion cell layer (GCL) and inner nuclear layer (INL) relative to wild-type; no differences are noted at 72 h after low-dose NMDA injection
  • at higher doses of NMDA, homozygotes show no differences in retinal damage 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 resistance to induced retinal damage (MGI Ref ID J:93533)
  • homozygotes are partially resistant to NMDA-induced retinal damage relative to wild-type mice
  • in contrast, neither intravitreal kainic acid nor transient ischemia results in significant differences in retinal damage in mutant vs. wild-type mice
• nervous system phenotype
• decreased cerebral infarction size (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 significantly smaller than that produced in wild-type mice
• intracerebral hemorrhage (MGI Ref ID J:89052)
  • in a photothrombotic model of middle cerebral artery occlusion (MCAO), delayed heparin administration increases cerebral hemorrhage associated with ischemia in wild-type but NOT in mutant mice
  • in this MCAO model, heparin administration induces tPA activity and mRNA expression in microglial cells, and enhances MMP9 expression and proteolytic activation in the ischemic brains of wild-type but NOT of mutant mice
• homeostasis/metabolism phenotype
• abnormal fibrinogen physiology (MGI Ref ID J:82604)
  • 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
  • after bleomycin treatment, homozygotes exhibit areas of fibrin(ogen) deposits, especially in the vasculature of the lung, where fibrin thrombi are observed
• decreased cerebral infarction size (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 significantly smaller than that produced in wild-type mice
• reduced thrombolysis (MGI Ref ID J:17427)
  • homozygotes exhibit a significant reduction in the rate of lysis of 125I-fibrin-labeled pulmonary plasma clots relative to wild-type mice
• thrombosis (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 (76% versus 54%) and to a much larger extent than wild-type mice (55% of mutants show >4 thrombosed veins per tissue section versus only 15% in wild-type)

Plat^tm1Mlg/Plat^tm1Mlg

        involves: 129S2/SvPas * C57BL/6J

• cardiovascular system phenotype
• decreased angiogenesis (MGI Ref ID J:108675)
  • aortic vessel explants show almost complete inhibition of capillary sprouting in both collagen lattices and Matrigel

View Research Applications

Research Applications

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

Plat^tm1Mlg related

Hematological Research
Clotting Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Plattm1Mlg
Allele Name		targeted mutation 1, Richard C Mulligan
Allele Type		Targeted (knock-out)
Common Name(s)		Plattm1; t-PA-; tPA-;
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		Plat, plasminogen activator, tissue
Chromosome		8
Gene Common Name(s)		AU020998; AW212668; D8Ertd2e; DKFZp686I03148; DNA segment, Chr 8, ERATO Doi 2, expressed; MGC:18508; PATISS; T-PA; TPA; expressed sequence AU020998; expressed sequence AW212668;
Molecular Note		The gene was disrupted using neomycin resistance cassette. The vector replaced genomic sequences encoding most of the kringle-2 domain and part of the proteinase domain, including the catalytically essential histidine residue at position 326. Targeting was confirmed by the absence of gene specific mRNA and immunoreactivity. [MGI Ref ID J:17427]

Genotyping

Genotyping Information

Genotyping Protocols

Plat^tm1Mlg, STD PCR, vers. 1

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

Centonze D; Napolitano M; Saulle E; Gubellini P; Picconi B; Martorana A; Pisani A; Gulino A; Bernardi G; Calabresi P. 2002. Tissue plasminogen activator is required for corticostriatal long-term potentiation. Eur J Neurosci 16(4):713-21. [PubMed: 12270047]  [MGI Ref ID J:89414]

Huang YY; Bach ME; Lipp HP; Zhuo M; Wolfer DP; Hawkins RD; Schoonjans L; Kandel ER; Godfraind JM; Mulligan R; Collen D; Carmeliet P. 1996. Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways. Proc Natl Acad Sci U S A 93(16):8699-704. [PubMed: 8710934]  [MGI Ref ID J:34823]

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 T; Yamada K; Yoshimura M; Ishikawa K; Miyamoto Y; Hashimoto K; Noda Y; Nitta A; Nabeshima T. 2004. The tissue plasminogen activator-plasmin system participates in the rewarding effect of morphine by regulating dopamine release. Proc Natl Acad Sci U S A 101(10):3650-5. [PubMed: 14988509]  [MGI Ref ID J:88913]

Plat^tm1Mlg related

Adhami F; Yu D; Yin W; Schloemer A; Burns KA; Liao G; Degen JL; Chen J; Kuan CY. 2008. Deleterious effects of plasminogen activators in neonatal cerebral hypoxia-ischemia. Am J Pathol 172(6):1704-16. [PubMed: 18467699]  [MGI Ref ID J:136189]

Ammassari-Teule M; Restivo L; Pietteur V; Passino E. 2001. Learning about the context in genetically-defined mice. Behav Brain Res 125(1-2):195-204. [PubMed: 11682111]  [MGI Ref ID J:92773]

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]

Bennur S; Shankaranarayana Rao BS; Pawlak R; Strickland S; McEwen BS; Chattarji S. 2007. Stress-induced spine loss in the medial amygdala is mediated by tissue-plasminogen activator. Neuroscience 144(1):8-16. [PubMed: 17049177]  [MGI Ref ID J:117942]

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]

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

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

Calabresi P; Napolitano M; Centonze D; Marfia GA; Gubellini P; Teule MA; Berretta N; Bernardi G; Frati L; Tolu M; Gulino A. 2000. Tissue plasminogen activator controls multiple forms of synaptic plasticity and memory. Eur J Neurosci 12(3):1002-12. [PubMed: 10762331]  [MGI Ref ID J:89431]

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]

Centonze D; Napolitano M; Saulle E; Gubellini P; Picconi B; Martorana A; Pisani A; Gulino A; Bernardi G; Calabresi P. 2002. Tissue plasminogen activator is required for corticostriatal long-term potentiation. Eur J Neurosci 16(4):713-21. [PubMed: 12270047]  [MGI Ref ID J:89414]

Chen ZL; Indyk JA; Bugge TH; Kombrinck KW; Degen JL; Strickland S. 1999. Neuronal death and blood-brain barrier breakdown after excitotoxic injury are independent processes. J Neurosci 19(22):9813-20. [PubMed: 10559390]  [MGI Ref ID J:119842]

Chen ZL; Indyk JA; Strickland S. 2003. The hippocampal laminin matrix is dynamic and critical for neuronal survival. Mol Biol Cell 14(7):2665-76. [PubMed: 12857855]  [MGI Ref ID J:126217]

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]

East E; Baker D; Pryce G; Lijnen HR; Cuzner ML; Gveric D. 2005. A Role for the Plasminogen Activator System in Inflammation and Neurodegeneration in the Central Nervous System during Experimental Allergic Encephalomyelitis. Am J Pathol 167(2):545-54. [PubMed: 16049338]  [MGI Ref ID J:99944]

Frey U; Muller M; Kuhl D. 1996. A different form of long-lasting potentiation revealed in tissue plasminogen activator mutant mice. J Neurosci 16(6):2057-63. [PubMed: 8604050]  [MGI Ref ID J:110861]

Fukakusa A; Nagai T; Mizoguchi H; Otsuka N; Kimura H; Kamei H; Kim HC; Nabeshima T; Takuma K; Yamada K. 2008. Role of tissue plasminogen activator in the sensitization of methamphetamine-induced dopamine release in the nucleus accumbens. J Neurochem 105(2):436-44. [PubMed: 18036193]  [MGI Ref ID J:135451]

Hennebert O; Laudenbach V; Laquerriere A; Verney C; Carmeliet P; Marret S; Leroux P. 2005. Ontogenic study of the influence of tissue plasminogen activator (t-PA) in neonatal excitotoxic brain insult and the subsequent microglia/macrophage activation. Neuroscience 130(3):697-712. [PubMed: 15590153]  [MGI Ref ID J:105225]

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]

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]

Horwood JM; Ripley TL; Stephens DN. 2004. Evidence for disrupted NMDA receptor function in tissue plasminogen activator knockout mice. Behav Brain Res 150(1-2):127-38. [PubMed: 15033286]  [MGI Ref ID J:95936]

Hu K; Wu C; Mars WM; Liu Y. 2007. Tissue-type plasminogen activator promotes murine myofibroblast activation through LDL receptor-related protein 1-mediated integrin signaling. J Clin Invest 117(12):3821-32. [PubMed: 18037995]  [MGI Ref ID J:130749]

Huang YY; Bach ME; Lipp HP; Zhuo M; Wolfer DP; Hawkins RD; Schoonjans L; Kandel ER; Godfraind JM; Mulligan R; Collen D; Carmeliet P. 1996. Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways. Proc Natl Acad Sci U S A 93(16):8699-704. [PubMed: 8710934]  [MGI Ref ID J:34823]

Ito M; Nagai T; Mizoguchi H; Fukakusa A; Nakanishi Y; Kamei H; Nabeshima T; Takuma K; Yamada K. 2007. Possible involvement of protease-activated receptor-1 in the regulation of morphine-induced dopamine release and hyperlocomotion by the tissue plasminogen activator-plasmin system. J Neurochem 101(5):1392-9. [PubMed: 17286591]  [MGI Ref ID J:122545]

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]

Kumada M; Niwa M; Wang X; Matsuno H; Hara A; Mori H; Matsuo O; Yamamoto T; Kozawa O. 2004. Endogenous tissue type plasminogen activator facilitates NMDA-induced retinal damage. Toxicol Appl Pharmacol 200(1):48-53. [PubMed: 15451307]  [MGI Ref ID J:93533]

Lee SR; Lok J; Rosell A; Kim HY; Murata Y; Atochin D; Huang PL; Wang X; Ayata C; Moskowitz MA; Lo EH. 2007. Reduction of hippocampal cell death and proteolytic responses in tissue plasminogen activator knockout mice after transient global cerebral ischemia. Neuroscience 150(1):50-7. [PubMed: 17936515]  [MGI Ref ID J:130793]

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]

Leroux P; Hennebert O; Legros H; Laudenbach V; Carmeliet P; Marret S. 2007. Role of tissue-plasminogen activator (t-PA) in a mouse model of neonatal white matter lesions: interaction with plasmin inhibitors and anti-inflammatory drugs. Neuroscience 146(2):670-8. [PubMed: 17321054]  [MGI Ref ID J:122015]

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]

Ling C; Zou T; Hsiao Y; Tao X; Chen ZL; Strickland S; Song H. 2006. Disruption of tissue plasminogen activator gene reduces macrophage migration. Biochem Biophys Res Commun 349(3):906-12. [PubMed: 16978586]  [MGI Ref ID J:113092]

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]

Lu W; Bhasin M; Tsirka SE. 2002. Involvement of tissue plasminogen activator in onset and effector phases of experimental allergic encephalomyelitis. J Neurosci 22(24):10781-9. [PubMed: 12486171]  [MGI Ref ID J:109204]

Lu W; Tsirka SE. 2002. Partial rescue of neural apoptosis in the Lurcher mutant mouse through elimination of tissue plasminogen activator. Development 129(8):2043-50. [PubMed: 11934869]  [MGI Ref ID J:111363]

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]

Mataga N; Mizuguchi Y; Hensch TK. 2004. Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator. Neuron 44(6):1031-41. [PubMed: 15603745]  [MGI Ref ID J:107754]

Mataga N; Nagai N; Hensch TK. 2002. Permissive proteolytic activity for visual cortical plasticity. Proc Natl Acad Sci U S A 99(11):7717-21. [PubMed: 12032349]  [MGI Ref ID J:109699]

Matys T; Pawlak R; Matys E; Pavlides C; McEwen BS; Strickland S. 2004. Tissue plasminogen activator promotes the effects of corticotropin-releasing factor on the amygdala and anxiety-like behavior. Proc Natl Acad Sci U S A 101(46):16345-50. [PubMed: 15522965]  [MGI Ref ID J:94733]

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]

Mecenas PE; Tsirka SE; Salles F; Strickland S. 1997. Removal of tissue plasminogen activator does not protect against neuronal degeneration in the cerebellum of the weaver mouse. Brain Res 772(1-2):233-8. [PubMed: 9406977]  [MGI Ref ID J:44005]

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 T; Ito M; Nakamichi N; Mizoguchi H; Kamei H; Fukakusa A; Nabeshima T; Takuma K; Yamada K. 2006. The rewards of nicotine: regulation by tissue plasminogen activator-plasmin system through protease activated receptor-1. J Neurosci 26(47):12374-83. [PubMed: 17122062]  [MGI Ref ID J:116177]

Nagai T; Noda Y; Ishikawa K; Miyamoto Y; Yoshimura M; Ito M; Takayanagi M; Takuma K; Yamada K; Nabeshima T. 2005. The role of tissue plasminogen activator in methamphetamine-related reward and sensitization. J Neurochem 92(3):660-7. [PubMed: 15659235]  [MGI Ref ID J:105137]

Nagai T; Yamada K; Yoshimura M; Ishikawa K; Miyamoto Y; Hashimoto K; Noda Y; Nitta A; Nabeshima T. 2004. The tissue plasminogen activator-plasmin system participates in the rewarding effect of morphine by regulating dopamine release. Proc Natl Acad Sci U S A 101(10):3650-5. [PubMed: 14988509]  [MGI Ref ID J:88913]

Norris EH; Strickland S. 2007. Modulation of NR2B-regulated contextual fear in the hippocampus by the tissue plasminogen activator system. Proc Natl Acad Sci U S A 104(33):13473-8. [PubMed: 17673549]  [MGI Ref ID J:123767]

Ny A; Nordstrom L; Carmeliet P; Ny T. 1997. Studies of mice lacking plasminogen activator gene function suggest that plasmin production prior to ovulation exceeds the amount needed for optimal ovulation efficiency. Eur J Biochem 244(2):487-93. [PubMed: 9119016]  [MGI Ref ID J:39196]

Pang PT; Teng HK; Zaitsev E; Woo NT; Sakata K; Zhen S; Teng KK; Yung WH; Hempstead BL; Lu B. 2004. Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 306(5695):487-91. [PubMed: 15486301]  [MGI Ref ID J:105428]

Parathath SR; Parathath S; Tsirka SE. 2006. Nitric oxide mediates neurodegeneration and breakdown of the blood-brain barrier in tPA-dependent excitotoxic injury in mice. J Cell Sci 119(Pt 2):339-49. [PubMed: 16410551]  [MGI Ref ID J:105390]

Pawlak R; Magarinos AM; Melchor J; McEwen B; Strickland S. 2003. Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior. Nat Neurosci 6(2):168-74. [PubMed: 12524546]  [MGI Ref ID J:81694]

Pawlak R; Melchor JP; Matys T; Skrzypiec AE; Strickland S. 2005. Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors. Proc Natl Acad Sci U S A 102(2):443-8. [PubMed: 15630096]  [MGI Ref ID J:96253]

Pawlak R; Nagai N; Urano T; Napiorkowska-Pawlak D; Ihara H; Takada Y; Collen D; Takada A. 2002. Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator on hippocampus-dependent learning in mice. Neuroscience 113(4):995-1001. [PubMed: 12182903]  [MGI Ref ID J:120677]

Pawlak R; Rao BS; Melchor JP; Chattarji S; McEwen B; Strickland S. 2005. Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Proc Natl Acad Sci U S A 102(50):18201-6. [PubMed: 16330749]  [MGI Ref ID J:104368]

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]

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]

Renckens R; Roelofs JJ; Florquin S; de Vos AF; Pater JM; Lijnen HR; Carmeliet P; van 't Veer C; van der Poll T. 2006. Endogenous tissue-type plasminogen activator is protective during Escherichia coli-induced abdominal sepsis in mice. J Immunol 177(2):1189-96. [PubMed: 16818777]  [MGI Ref ID J:134991]

Ripley TL; Horwood JM; Stephens DN. 2001. Evidence for impairment of behavioural inhibition in performance of operant tasks in tPA-/- mice. Behav Brain Res 125(1-2):215-27. [PubMed: 11682113]  [MGI Ref ID J:96450]

Ripley TL; Rocha BA; Oglesby MW; Stephens DN. 1999. Increased sensitivity to cocaine, and over-responding during cocaine self-administration in tPA knockout mice. Brain Res 826(1):117-27. [PubMed: 10216203]  [MGI Ref ID J:107785]

Sachs BD; Baillie GS; McCall JR; Passino MA; Schachtrup C; Wallace DA; Dunlop AJ; MacKenzie KF; Klussmann E; Lynch MJ; Sikorski SL; Nuriel T; Tsigelny I; Zhang J; Houslay MD; Chao MV; Akassoglou K. 2007. p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway. J Cell Biol 177(6):1119-32. [PubMed: 17576803]  [MGI Ref ID J:134923]

Samara GJ; Schaffner AD; Eisenstat J; Nguyen HL. 2004. The effects of the plasminogen pathway on scar tissue formation. Laryngoscope 114(1):46-9. [PubMed: 14709993]  [MGI Ref ID J:105270]

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]

Schaefer U; Machida T; Vorlova S; Strickland S; Levi R. 2006. The plasminogen activator system modulates sympathetic nerve function. J Exp Med 203(9):2191-200. [PubMed: 16940168]  [MGI Ref ID J:124557]

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]

Seeds NW; Basham ME; Ferguson JE. 2003. Absence of tissue plasminogen activator gene or activity impairs mouse cerebellar motor learning. J Neurosci 23(19):7368-75. [PubMed: 12917371]  [MGI Ref ID J:84875]

Seeds NW; Basham ME; Haffke SP. 1999. Neuronal migration is retarded in mice lacking the tissue plasminogen activator gene. Proc Natl Acad Sci U S A 96(24):14118-23. [PubMed: 10570208]  [MGI Ref ID J:58684]

Sheehan JJ; Zhou C; Gravanis I; Rogove AD; Wu YP; Bogenhagen DF; Tsirka SE. 2007. Proteolytic activation of monocyte chemoattractant protein-1 by plasmin underlies excitotoxic neurodegeneration in mice. J Neurosci 27(7):1738-45. [PubMed: 17301181]  [MGI Ref ID J:141739]

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]

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]

Tsirka SE; Gualandris A; Amaral DG; Strickland S. 1995. Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 377(6547):340-4. [PubMed: 7566088]  [MGI Ref ID J:28943]

Tsirka SE; Rogove AD; Bugge TH; Degen JL; Strickland S. 1997. An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J Neurosci 17(2):543-52. [PubMed: 8987777]  [MGI Ref ID J:37549]

Tsuji K; Aoki T; Tejima E; Arai K; Lee SR; Atochin DN; Huang PL; Wang X; Montaner J; Lo EH. 2005. Tissue plasminogen activator promotes matrix metalloproteinase-9 upregulation after focal cerebral ischemia. Stroke 36(9):1954-9. [PubMed: 16051896]  [MGI Ref ID J:114417]

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]

Yan Y; Yamada K; Mizoguchi H; Noda Y; Nagai T; Nitta A; Nabeshima T. 2007. Reinforcing effects of morphine are reduced in tissue plasminogen activator-knockout mice. Neuroscience 146(1):50-9. [PubMed: 17317018]  [MGI Ref ID J:122016]

Yang J; Shultz RW; Mars WM; Wegner RE; Li Y; Dai C; Nejak K; Liu Y. 2002. Disruption of tissue-type plasminogen activator gene in mice reduces renal interstitial fibrosis in obstructive nephropathy. J Clin Invest 110(10):1525-38. [PubMed: 12438450]  [MGI Ref ID J:118424]

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; Coleman TA; Moore E; Wu JY; Mitola D; Bugge TH; Lawrence DA. 2002. Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent. J Clin Invest 109(12):1571-8. [PubMed: 12070304]  [MGI Ref ID J:120679]

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]

Zhang X; Polavarapu R; She H; Mao Z; Yepes M. 2007. Tissue-type plasminogen activator and the low-density lipoprotein receptor-related protein mediate cerebral ischemia-induced nuclear factor-kappaB pathway activation. Am J Pathol 171(4):1281-90. [PubMed: 17717150]  [MGI Ref ID J:125519]

Zhang Y; Kanaho Y; Frohman MA; Tsirka SE. 2005. Phospholipase D1-promoted release of tissue plasminogen activator facilitates neurite outgrowth. J Neurosci 25(7):1797-805. [PubMed: 15716416]  [MGI Ref ID J:98242]

Zhao BQ; Ikeda Y; Ihara H; Urano T; Fan W; Mikawa S; Suzuki Y; Kondo K; Sato K; Nagai N; Umemura K. 2004. Essential role of endogenous tissue plasminogen activator through matrix metalloproteinase 9 induction and expression on heparin-produced cerebral hemorrhage after cerebral ischemia in mice. Blood 103(7):2610-6. [PubMed: 14630814]  [MGI Ref ID J:89052]

Zhuo M; Holtzman DM; Li Y; Osaka H; DeMaro J; Jacquin M; Bu G. 2000. Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation. J Neurosci 20(2):542-9. [PubMed: 10632583]  [MGI Ref ID J:120571]

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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

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

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Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

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

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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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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.