Register New MMRRC Account
Reset Password
Register for New Mouse Models
Click Here for Additional Contact Information
Availability & Fees Order this Strain
The transgene consists of the mouse Plau gene under the control of the human scavenger receptor A promoter and enhancer, resulting in macrophage-specific transgene expression. mRNA expression is increased 40-fold and activity is elevated as much as 500-fold in stimulated peritoneal macrophages.
The Apoe allele is a knockout, where insertion of a neomycin resistance cassette deleted part of exon 3 and part of intron 3.
The transgene was injected into zygotes of C57BL/6 x SJL background. Founders were bred into the C57BL/6J ApoE-null background. Three founders were identified with macrophage-specific expression of the Plau transgene, of which Line #1 had the highest level of macrophage-specific expression (as well as elevated Plau expression in the atherosclerotic aorta). The transgene was backcrossed into the C57BL/6J background at least 6 times before the initial study was published (PMID:15096455)
Cozen AE, Moriwaki H, Kremen M, DeYoung MB, Dichek HL, Slezicki KI, Young SG, Véniant M, Dichek DA. Macrophage-targeted overexpression of urokinase causes accelerated atherosclerosis, coronary artery occlusions, and premature death. Circulation. 2004 May 4;109(17):2129-35. doi: 10.1161/01.CIR.0000127369.24127.03. Epub 2004 Apr 19. (Medline PMID: 15096455)
Moriwaki H, Stempien-Otero A, Kremen M, Cozen AE, Dichek DA. Overexpression of urokinase by macrophages or deficiency of plasminogen activator inhibitor type 1 causes cardiac fibrosis in mice. Circ Res. 2004 Sep 17;95(6):637-44. doi: 10.1161/01.RES.0000141427.61023.f4. Epub 2004 Aug 5. (Medline PMID: 15297377)
Stempien-Otero A, Plawman A, Meznarich J, Dyamenahalli T, Otsuka G, Dichek DA. Mechanisms of cardiac fibrosis induced by urokinase plasminogen activator. J Biol Chem. 2006 Jun 2;281(22):15345-51. doi: 10.1074/jbc.M512818200. Epub 2006 Mar 22. (Medline PMID: 16554301)
Carlson S, Helterline D, Asbe L, Dupras S, Minami E, Farris S, Stempien-Otero A. Cardiac macrophages adopt profibrotic/M2 phenotype in infarcted hearts: Role of urokinase plasminogen activator. J Mol Cell Cardiol. 2017 Jul;108:42-49. doi: 10.1016/j.yjmcc.2016.05.016. Epub 2016 Jun 1. (Medline PMID: 27262672)
Meznarich J, Malchodi L, Helterline D, Ramsey SA, Bertko K, Plummer T, Plawman A, Gold E, Stempien-Otero A. Urokinase plasminogen activator induces pro-fibrotic/m2 phenotype in murine cardiac macrophages. PLoS One. 2013;8(3):e57837. doi: 10.1371/journal.pone.0057837. Epub 2013 Mar 11. (Medline PMID: 23536772)
Minami E, Castellani C, Malchodi L, Deem J, Bertko K, Meznarich J, Dishmon M, Murry CE, Stempien-Otero A. The role of macrophage-derived urokinase plasminogen activator in myocardial infarct repair: urokinase attenuates ventricular remodeling. J Mol Cell Cardiol. 2010 Sep;49(3):516-24. doi: 10.1016/j.yjmcc.2010.03.022. Epub 2010 Apr 7. (Medline PMID: 20380835)
Hu JH, Du L, Chu T, Otsuka G, Dronadula N, Jaffe M, Gill SE, Parks WC, Dichek DA. Overexpression of urokinase by plaque macrophages causes histological features of plaque rupture and increases vascular matrix metalloproteinase activity in aged apolipoprotein e-null mice. Circulation. 2010 Apr 13;121(14):1637-44. doi: 10.1161/CIRCULATIONAHA.109.914945. Epub 2010 Mar 29. (Medline PMID: 20351234)
Vaisar T, Hu JH, Airhart N, Fox K, Heinecke J, Nicosia RF, Kohler T, Potter ZE, Simon GM, Dix MM, Cravatt BF, Gharib SA, Dichek DA. Parallel Murine and Human Plaque Proteomics Reveals Pathways of Plaque Rupture. Circ Res. 2020 Sep 25;127(8):997-1022. doi: 10.1161/CIRCRESAHA.120.317295. Epub 2020 Jul 30. (Medline PMID: 32762496)
Novak ML, Bryer SC, Cheng M, Nguyen MH, Conley KL, Cunningham AK, Xue B, Sisson TH, You JS, Hornberger TA, Koh TJ. Macrophage-specific expression of urokinase-type plasminogen activator promotes skeletal muscle regeneration. J Immunol. 2011 Aug 1;187(3):1448-57. doi: 10.4049/jimmunol.1004091. Epub 2011 Jun 27. (Medline PMID: 21709151)
Colony Surveillance Program and Current Health Reports
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.
The donor or their institution limits the distribution to non-profit institutions only.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.
Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.
1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.
4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.