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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) 01-MAR-06 Species laboratory mouse Generation N9+1F13N1F6 (29-SEP-08) Donating Investigator Colin Funk, Queen's University Description
Mice homozygous for the Alox5tm1Fun targeted mutation are viable and fertile. In general, homozygous mutant mice are selectively resistant to inflammatory insults. They are resistant to the lethal effects of platelet activating factor but reaction to endotoxin shock is normal. Phorbol ester induced inflammation is normal but arachidonic acid induced inflammation is reduced.Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the Alox5 gene. The construct was electroporated into 129S2/SvPas-derived D3H embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6J females.
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying Alox5tm1Fun allele
002485 129-Alox5tm1Fun/J 002263 B6;129S2-Alox5tm1Fun/J View Strains carrying Alox5tm1Fun (2 strains)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Alox5tm1Fun/Alox5tm1Fun
B6.Cg-Alox5tm1Fun
- immune system phenotype
- *normal* immune system phenotype (MGI Ref ID J:89268)
- homozygotes display no differences in infarct size following induction of focal cerebral ischemia (permanent or transient; 60 min) relative to wild-type
Alox5tm1Fun/Alox5tm1Fun
B6.129S2-Alox5tm1Fun/J
- adipose tissue phenotype
- increased total fat pad weight (MGI Ref ID J:104825)
- increased total fat pad weight
- homeostasis/metabolism phenotype
- increased circulating VLDL cholesterol level (MGI Ref ID J:104825)
- increased plasma VLDL/LDL cholesterol
- increased circulating leptin level (MGI Ref ID J:104825)
- skeleton phenotype
- increased bone density (MGI Ref ID J:104825)
- increased bone mineral density
- immune system phenotype
- decreased susceptibility to autoimmune disorder (MGI Ref ID J:108446)
- upon adoptive transfer of IRBP1-20-specific T cells from wild-type B6 donors to wild-type and Alox5-deficient recipients, wild-type mice develop severe clinical uveitis, whereas mutant recipients show only mild and transient clinical disease
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Alox5tm1Fun/Alox5tm1Fun
involves: 129S2/SvPas * C57BL/6
- cardiovascular system phenotype
- *normal* cardiovascular system phenotype (MGI Ref ID J:21372)
- homozygotes display a normal mean arterial pressure and heart rate relative to wild-type
- hematopoietic system phenotype
- *normal* hematopoietic system phenotype (MGI Ref ID J:21372)
- analysis of cell-surface markers CD3, CD4 and B220 on splenocytes from 4-wk- and 8-wk-old mice revealed no other abnormalities
- homozygotes show no changes in total blood cell populations or differential cell counts
- bone marrow analysis revealed no evidence of abnormal precursor cells of any lineage relative to wild-type
- small spleen (MGI Ref ID J:21372)
- homozygotes show no abnormalities up to 10 months of age under normal physiological conditions; however, their spleen is usually smaller relative to wild-type
- immune system phenotype
- *normal* immune system phenotype (MGI Ref ID J:21372)
- homozygotes display a normal reaction to endotoxin-induced shock
- also, homozygotes exhibit a normal reaction to ear inflammation induced by topical application of phorbol myristyl acetate
- neutrophil recruitment into the peritoneal cavity by a non-specific inflammatory challenge (glycogen) elicits a comparable (large) influx of polymorphonuclear leukocytes in both wild-type and mutant mice
- abnormal immune system physiology (MGI Ref ID J:21372)
- conscious, unanaesthetized homozygotes show resistance to the lethal effects of platelet-activating factor (PAF): they display the same listless behavior as wild-type for the first 20 min but recover quickly
- mechanically ventilated, anesthetized homozygotes show no signs of broncho-constriction; however, broncho-constriction is observed after methacholine challenge
- decreased inflammatory response (MGI Ref ID J:21372)
- homozygotes show a significantly reduced reaction to arachidonic acid-induced ear inflammation; administration of leukotrienes rescues this inflammatory phenotype: inflammation is rapid in onset and maximal swelling is reached between 30-60 min
- homozygotes display a significantly reduced chemotactic infiltration by polymorphonuclear leukocytes following induction of immune complex peritonitis (reverse passive Arthus reaction)
- in the thioglycollate-elicited peritonitis model, homozygotes only generate about 50% as much peritoneal leukocytosis as wild-type mice at 4.5 h after i.p. thioglycollate challenge; as expected, leukotriene B4 is absent from the mutant peritoneal fluid
- the specific arachidonate 5-lipoxygenase inhibitor, zileuton, has no effect on the peripheral white-cell count in mutant mice
- small spleen (MGI Ref ID J:21372)
- homozygotes show no abnormalities up to 10 months of age under normal physiological conditions; however, their spleen is usually smaller relative to wild-type
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Alox5tm1Fun related
Immunology and Inflammation Research
Inflammation
Metabolism Research
Enzyme Deficiency
| Allele Symbol | Alox5tm1Fun | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Colin Funk | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | 5-LO KO; 5-LO-; 5-LOX K/O; 5-LOX-; 5LX-; | ||
| Mutation Made By | Colin Funk, Queen's University | ||
| Strain of Origin | 129S2/SvPas | ||
| ES Cell Line Name | D3H | ||
| ES Cell Line Strain | 129S2/SvPas | ||
| Gene Symbol and Name | Alox5, arachidonate 5-lipoxygenase | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | 5-LO; 5-LOX; 5LO; 5LPG; 5LX; AI850497; LOG5; MGC163204; expressed sequence AI850497; | ||
| Molecular Note | Insertion of a neomycin resistance cassette into exon 6 disrupted the Alox5 gene. RT-PCR studies did not detect transcript in resident peritoneal macrophages of homozygous mutant mice. Western blot analysis of resident peritoneal macrophages of homozygous mutant mice did not detect ALOX5. [MGI Ref ID J:21372] | ||
Genotyping Protocols
Alox5tm1Fun, Standard PCR
Generic Neo Quantitative PCR-QPCR- 1.2, QPCR
Helpful Links
Genotyping resources and troubleshooting
Chen XS; Sheller JR; Johnson EN; Funk CD. 1994. Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene. Nature 372(6502):179-82. [PubMed: 7969451] [MGI Ref ID J:21372]
Kitagawa K; Matsumoto M; Hori M. 2004. Cerebral ischemia in 5-lipoxygenase knockout mice. Brain Res 1004(1-2):198-202. [PubMed: 15033436] [MGI Ref ID J:89268]
Alox5tm1Fun relatedAdamek A; Jung S; Dienesch C; Laser M; Ertl G; Bauersachs J; Frantz S. 2007. Role of 5-lipoxygenase in myocardial ischemia-reperfusion injury in mice. Eur J Pharmacol 571(1):51-4. [PubMed: 17586489] [MGI Ref ID J:136740]
Bafica A; Scanga CA; Serhan C; Machado F; White S; Sher A; Aliberti J. 2005. Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase-dependent lipoxin production. J Clin Invest 115(6):1601-1606. [PubMed: 15931391] [MGI Ref ID J:99199]
Bailie MB; Standiford TJ; Laichalk LL; Coffey MJ; Strieter R; Peters-Golden M. 1996. Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities. J Immunol 157(12):5221-4. [PubMed: 8955165] [MGI Ref ID J:110715]
Benjamim CF; Canetti C; Cunha FQ; Kunkel SL; Peters-Golden M. 2005. Opposing and hierarchical roles of leukotrienes in local innate immune versus vascular responses in a model of sepsis. J Immunol 174(3):1616-20. [PubMed: 15661924] [MGI Ref ID J:96404]
Canetti C; Aronoff DM; Choe M; Flamand N; Wettlaufer S; Toews GB; Chen GH; Peters-Golden M. 2006. Differential regulation by leukotrienes and calcium of Fc gamma receptor-induced phagocytosis and Syk activation in dendritic cells versus macrophages. J Leukoc Biol 79(6):1234-41. [PubMed: 16574771] [MGI Ref ID J:109680]
Cao RY; Adams MA; Habenicht AJ; Funk CD. 2007. Angiotensin II-induced abdominal aortic aneurysm occurs independently of the 5-lipoxygenase pathway in apolipoprotein E-deficient mice. Prostaglandins Other Lipid Mediat 84(1-2):34-42. [PubMed: 17643886] [MGI Ref ID J:129321]
Chen Y; Hu Y; Zhang H; Peng C; Li S. 2009. Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia. Nat Genet 41(7):783-92. [PubMed: 19503090] [MGI Ref ID J:151419]
Chen Y; Zhu J; Lum PY; Yang X; Pinto S; MacNeil DJ; Zhang C; Lamb J; Edwards S; Sieberts SK; Leonardson A; Castellini LW; Wang S; Champy MF; Zhang B; Emilsson V; Doss S; Ghazalpour A; Horvath S; Drake TA; Lusis AJ; Schadt EE. 2008. Variations in DNA elucidate molecular networks that cause disease. Nature 452(7186):429-35. [PubMed: 18344982] [MGI Ref ID J:134171]
Collin M; Rossi A; Cuzzocrea S; Patel NS; Di Paola R; Hadley J; Collino M; Sautebin L; Thiemermann C. 2004. Reduction of the multiple organ injury and dysfunction caused by endotoxemia in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton. J Leukoc Biol 76(5):961-70. [PubMed: 15328337] [MGI Ref ID J:93517]
Cuzzocrea S; Rossi A; Serraino I; Di Paola R; Dugo L; Genovese T; Britti D; Sciarra G; De Sarro A; Caputi AP; Sautebin L. 2003. 5-lipoxygenase knockout mice exhibit a resistance to acute pancreatitis induced by cerulein. Immunology 110(1):120-30. [PubMed: 12941149] [MGI Ref ID J:113639]
Cuzzocrea S; Rossi A; Serraino I; Mazzon E; Di Paola R; Dugo L; Genovese T; Calabro B; Caputi AP; Sautebin L. 2003. 5-Lipoxygenase knockout mice exhibit a resistance to pleurisy and lung injury caused by carrageenan. J Leukoc Biol 73(6):739-46. [PubMed: 12773506] [MGI Ref ID J:120440]
DiMeo D; Tian J; Zhang J; Narushima S; Berg DJ. 2008. Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase. Immunology 123(2):250-62. [PubMed: 17894798] [MGI Ref ID J:134808]
Emerson MR; LeVine SM. 2004. Experimental allergic encephalomyelitis is exacerbated in mice deficient for 12/15-lipoxygenase or 5-lipoxygenase. Brain Res 1021(1):140-5. [PubMed: 15328042] [MGI Ref ID J:92011]
Firuzi O; Zhuo J; Chinnici CM; Wisniewski T; Pratico D. 2008. 5-Lipoxygenase gene disruption reduces amyloid-beta pathology in a mouse model of Alzheimer's disease. FASEB J 22(4):1169-78. [PubMed: 17998412] [MGI Ref ID J:134897]
Genovese T; Mazzon E; Rossi A; Di Paola R; Cannavo G; Muia C; Crisafulli C; Bramanti P; Sautebin L; Cuzzocrea S. 2005. Involvement of 5-lipoxygenase in spinal cord injury. J Neuroimmunol 166(1-2):55-64. [PubMed: 16019083] [MGI Ref ID J:106400]
Ghazalpour A; Wang X; Lusis AJ; Mehrabian M. 2006. Complex inheritance of the 5-lipoxygenase locus influencing atherosclerosis in mice. Genetics 173(2):943-51. [PubMed: 16624897] [MGI Ref ID J:109792]
Gubitosi-Klug RA; Talahalli R; Du Y; Nadler JL; Kern TS. 2008. 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy. Diabetes 57(5):1387-93. [PubMed: 18346986] [MGI Ref ID J:136092]
Guerrero AT; Verri WA Jr; Cunha TM; Silva TA; Schivo IR; Dal-Secco D; Canetti C; Rocha FA; Parada CA; Cunha FQ; Ferreira SH. 2008. Involvement of LTB4 in zymosan-induced joint nociception in mice: participation of neutrophils and PGE2. J Leukoc Biol 83(1):122-30. [PubMed: 17913976] [MGI Ref ID J:130113]
Ichinose F; Zapol WM; Sapirstein A; Ullrich R; Tager AM; Coggins K; Jones R; Bloch KD. 2001. Attenuation of hypoxic pulmonary vasoconstriction by endotoxemia requires 5-lipoxygenase in mice. Circ Res 88(8):832-8. [PubMed: 11325876] [MGI Ref ID J:115401]
Irvin CG; Tu YP; Sheller JR; Funk CD. 1997. 5-Lipoxygenase products are necessary for ovalbumin-induced airway responsiveness in mice. Am J Physiol 272(6 Pt 1):L1053-8. [PubMed: 9227503] [MGI Ref ID J:113047]
Jiang W; Hall SR; Moos MP; Cao RY; Ishii S; Ogunyankin KO; Melo LG; Funk CD. 2008. Endothelial Cysteinyl Leukotriene 2 Receptor Expression Mediates Myocardial Ischemia-Reperfusion Injury. Am J Pathol 172(3):592-602. [PubMed: 18276782] [MGI Ref ID J:132275]
Kitagawa K; Matsumoto M; Hori M. 2004. Cerebral ischemia in 5-lipoxygenase knockout mice. Brain Res 1004(1-2):198-202. [PubMed: 15033436] [MGI Ref ID J:89268]
Lemos HP; Grespan R; Vieira SM; Cunha TM; Verri WA Jr; Fernandes KS; Souto FO; McInnes IB; Ferreira SH; Liew FY; Cunha FQ. 2009. Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFNgamma production. Proc Natl Acad Sci U S A 106(14):5954-9. [PubMed: 19289819] [MGI Ref ID J:147573]
Liao T; Ke Y; Shao WH; Haribabu B; Kaplan HJ; Sun D; Shao H. 2006. Blockade of the interaction of leukotriene b4 with its receptor prevents development of autoimmune uveitis. Invest Ophthalmol Vis Sci 47(4):1543-9. [PubMed: 16565390] [MGI Ref ID J:108446]
Machado ER; Ueta MT; Lourenco EV; Anibal FF; Sorgi CA; Soares EG; Roque-Barreira MC; Medeiros AI; Faccioli LH. 2005. Leukotrienes play a role in the control of parasite burden in murine strongyloidiasis. J Immunol 175(6):3892-9. [PubMed: 16148135] [MGI Ref ID J:116694]
McKee AS; Munks MW; MacLeod MK; Fleenor CJ; Van Rooijen N; Kappler JW; Marrack P. 2009. Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J Immunol 183(7):4403-14. [PubMed: 19734227] [MGI Ref ID J:152787]
Medeiros AI; Sa-Nunes A; Turato WM; Secatto A; Frantz FG; Sorgi CA; Serezani CH; Deepe GS Jr; Faccioli LH. 2008. Leukotrienes are potent adjuvant during fungal infection: effects on memory T cells. J Immunol 181(12):8544-51. [PubMed: 19050273] [MGI Ref ID J:142061]
Mehrabian M; Allayee H; Stockton J; Lum PY; Drake TA; Castellani LW; Suh M; Armour C; Edwards S; Lamb J; Lusis AJ; Schadt EE. 2005. Integrating genotypic and expression data in a segregating mouse population to identify 5-lipoxygenase as a susceptibility gene for obesity and bone traits. Nat Genet 37(11):1224-33. [PubMed: 16200066] [MGI Ref ID J:104825]
Mehrabian M; Allayee H; Wong J; Shi W; Wang XP; Shaposhnik Z; Funk CD; Lusis AJ. 2002. Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in mice. Circ Res 91(2):120-6. [PubMed: 12142344] [MGI Ref ID J:109703]
Mehrabian M; Schulthess FT; Nebohacova M; Castellani LW; Zhou Z; Hartiala J; Oberholzer J; Lusis AJ; Maedler K; Allayee H. 2008. Identification of ALOX5 as a gene regulating adiposity and pancreatic function. Diabetologia 51(6):978-88. [PubMed: 18421434] [MGI Ref ID J:137920]
Narushima S; DiMeo D; Tian J; Zhang J; Liu D; Berg DJ. 2008. 5-Lipoxygenase-derived lipid mediators are not required for the development of NSAID-induced inflammatory bowel disease in IL-10-/- mice. Am J Physiol Gastrointest Liver Physiol 294(2):G477-88. [PubMed: 18048478] [MGI Ref ID J:132202]
Peebles RS Jr; Hashimoto K; Sheller JR; Moore ML; Morrow JD; Ji S; Elias JA; Goleniewska K; O'neal J; Mitchell DB; Graham BS; Zhou W. 2005. Allergen-induced airway hyperresponsiveness mediated by cyclooxygenase inhibition is not dependent on 5-lipoxygenase or IL-5, but is IL-13 dependent. J Immunol 175(12):8253-9. [PubMed: 16339565] [MGI Ref ID J:122257]
Peters-Golden M; Bailie M; Marshall T; Wilke C; Phan SH; Toews GB; Moore BB. 2002. Protection from pulmonary fibrosis in leukotriene-deficient mice. Am J Respir Crit Care Med 165(2):229-35. [PubMed: 11790660] [MGI Ref ID J:103107]
Poeckel D; Zemski Berry KA; Murphy RC; Funk CD. 2009. Dual 12/15- and 5-lipoxygenase deficiency in macrophages alters arachidonic acid metabolism and attenuates peritonitis and atherosclerosis in apoe knock-out mice. J Biol Chem 284(31):21077-89. [PubMed: 19509298] [MGI Ref ID J:153174]
Rossi A; Acquaviva AM; Iuliano F; Di Paola R; Cuzzocrea S; Sautebin L. 2005. Up-regulation of prostaglandin biosynthesis by leukotriene C4 in elicited mice peritoneal macrophages activated with lipopolysaccharide/interferon-{gamma}. J Leukoc Biol 78(4):985-91. [PubMed: 16046553] [MGI Ref ID J:101535]
Segal BH; Kuhns DB; Ding L; Gallin JI; Holland SM. 2002. Thioglycollate peritonitis in mice lacking C5, 5-lipoxygenase, or p47(phox): complement, leukotrienes, and reactive oxidants in acute inflammation. J Leukoc Biol 71(3):410-6. [PubMed: 11867678] [MGI Ref ID J:75371]
Serezani CH; Aronoff DM; Jancar S; Mancuso P; Peters-Golden M. 2005. Leukotrienes enhance the bactericidal activity of alveolar macrophages against Klebsiella pneumoniae through the activation of NADPH oxidase. Blood 106(3):1067-75. [PubMed: 15718414] [MGI Ref ID J:117309]
Serezani CH; Aronoff DM; Jancar S; Peters-Golden M. 2005. Leukotriene B4 mediates p47phox phosphorylation and membrane translocation in polyunsaturated fatty acid-stimulated neutrophils. J Leukoc Biol 78(4):976-84. [PubMed: 16006535] [MGI Ref ID J:101536]
Serezani CH; Perrela JH; Russo M; Peters-Golden M; Jancar S. 2006. Leukotrienes are essential for the control of Leishmania amazonensis infection and contribute to strain variation in susceptibility. J Immunol 177(5):3201-8. [PubMed: 16920959] [MGI Ref ID J:139527]
Shim YM; Zhu Z; Zheng T; Lee CG; Homer RJ; Ma B; Elias JA. 2006. Role of 5-lipoxygenase in IL-13-induced pulmonary inflammation and remodeling. J Immunol 177(3):1918-24. [PubMed: 16849505] [MGI Ref ID J:138359]
Sorgi CA; Secatto A; Fontanari C; Turato WM; Belanger C; de Medeiros AI; Kashima S; Marleau S; Covas DT; Bozza PT; Faccioli LH. 2009. Histoplasma capsulatum cell wall {beta}-glucan induces lipid body formation through CD18, TLR2, and dectin-1 receptors: correlation with leukotriene B4 generation and role in HIV-1 infection. J Immunol 182(7):4025-35. [PubMed: 19299700] [MGI Ref ID J:147134]
Swindle EJ; Coleman JW; DeLeo FR; Metcalfe DD. 2007. FcepsilonRI- and Fcgamma receptor-mediated production of reactive oxygen species by mast cells is lipoxygenase- and cyclooxygenase-dependent and NADPH oxidase-independent. J Immunol 179(10):7059-71. [PubMed: 17982097] [MGI Ref ID J:153854]
Uz T; Dimitrijevic N; Imbesi M; Manev H; Manev R. 2008. Effects of MK-886, a 5-lipoxygenase activating protein (FLAP) inhibitor, and 5-lipoxygenase deficiency on the forced swimming behavior of mice. Neurosci Lett 436(2):269-72. [PubMed: 18403121] [MGI Ref ID J:136638]
Verri WA Jr; Cunha TM; Ferreira SH; Wei X; Leung BP; Fraser A; McInnes IB; Liew FY; Cunha FQ. 2007. IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. Eur J Immunol 37(12):3373-80. [PubMed: 17979156] [MGI Ref ID J:128427]
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry This strain originated on a B6;129S2 background and has been backcrossed to C57BL/6J for at least nine generations(8/21/01). Coat color expected from breeding:Black Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $111.30 Female or Male Homozygous for Alox5tm1Fun
Pairs /Price (US dollars $) Pair Genotype $222.60 Homozygous for Alox5tm1Fun x Homozygous for Alox5tm1Fun
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $144.70 Female or Male Homozygous for Alox5tm1Fun
Pairs /Price (US dollars $) Pair Genotype $289.40 Homozygous for Alox5tm1Fun x Homozygous for Alox5tm1Fun
| Standard Supply | 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 approximately 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 two business days following order placement. |
|---|---|
| Supply Notes |
|
| 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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