Description

Strain Information

Former Names B6.129P2-Scya3tm1Unc    (Changed: 15-DEC-04 ) 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/6J Donor Strain 129P2 via E14TG2a ES cell line Generation [N7F16p]N1F15 (18-DEC-08)   Donating Investigator Oliver Smithies,   University of North Carolina

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Scya3^tm1Unc targeted mutation are viable and fertile. Homozygous mutant mice are resistant to Coxsakievirus-induced myocarditis. Mutant mice infected with influenza virus show reduced pneumonitis and delayed clearance of virus. There are no overt hematopoietic abnormalities. Also known as macrophage inflammatory protein 1a, Mip1a.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ccl3^tm1Unc/Ccl3^tm1Unc

        B6.129P2-Ccl3^tm1Unc/J

• hematopoietic system phenotype
• decreased neutrophil cell number (MGI Ref ID J:94599)
  • 13-28% decrease in the number of infiltrating neutrophils in the skin at 4 and 8 hours after immune complex challenge compared to wild-type
• immune system phenotype
• decreased neutrophil cell number (MGI Ref ID J:94599)
  • 13-28% decrease in the number of infiltrating neutrophils in the skin at 4 and 8 hours after immune complex challenge compared to wild-type
• decreased susceptibility to type III hypersensitivity reaction (MGI Ref ID J:94599)
  • 20% reduction in edema, but no difference in hemorrhage, when cutaneous reverse passive Arthus reaction was induced compared to wild-type

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

Ccl3^tm1Unc/Ccl3^tm1Unc

        involves: 129P2/OlaHsd

• immune system phenotype
• decreased susceptibility to viral infection (MGI Ref ID J:28704)
  • resistance to Coxsackie virus-induced myocarditis and reduced pneumonitis after infection with influenza virus

View Research Applications

Research Applications

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

Ccl3^tm1Unc related

Cancer Research
Growth Factors/Receptors/Cytokines

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Inflammation

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ccl3tm1Unc
Allele Name		targeted mutation 1, University of North Carolina
Allele Type		Targeted (knock-out)
Common Name(s)		MIP-1alpha -; Scya3 -; Scya3tm1Coo;
Mutation Made By		Oliver Smithies,   University of North Carolina
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Ccl3, chemokine (C-C motif) ligand 3
Chromosome		11
Gene Common Name(s)		AI323804; G0S19-1; LD78ALPHA; MIP-1 alpha; MIP-1-alpha; MIP-1a; MIP-1alpha; MIP1-(a); MIP1-alpha; MIP1A; Mip1a; SCYA3; Scya3; expressed sequence AI323804; macrophage inflammatory protein-1 alpha; macrophage inflammatory protein-1alpha; small inducible cytokine A3;
Molecular Note		A neomycin selection cassette was used to delete a region including 300 nucleotides of the 5' untranslated region, all of exon 1, and a portion of exon 2. An absence of transcript was observed via Northern blot analysis of total mRNA derived from bone marrow macrophages isolated from homozygous mutant animals. [MGI Ref ID J:28704]

Genotyping

Genotyping Information

Genotyping Protocols

Ccl3^tm1Unc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Cook DN; Beck MA; Coffman TM; Kirby SL; Sheridan JF; Pragnell IB; Smithies O. 1995. Requirement of MIP-1 alpha for an inflammatory response to viral infection. Science 269(5230):1583-5. [PubMed: 7667639]  [MGI Ref ID J:28704]

Additional References

Salazar-Mather TP; Lewis CA; Biron CA. 2002. Type I interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1alpha delivery to the liver. J Clin Invest 110(3):321-30. [PubMed: 12163451]  [MGI Ref ID J:78321]

Wu YP; Proia RL. 2004. Deletion of macrophage-inflammatory protein 1 alpha retards neurodegeneration in Sandhoff disease mice. Proc Natl Acad Sci U S A 101(22):8425-30. [PubMed: 15155903]  [MGI Ref ID J:90687]

Ccl3^tm1Unc related

Ajuebor MN; Hogaboam CM; Le T; Proudfoot AE; Swain MG. 2004. CCL3/MIP-1alpha is pro-inflammatory in murine T cell-mediated hepatitis by recruiting CCR1-expressing CD4(+) T cells to the liver. Eur J Immunol 34(10):2907. [PubMed: 15368307]  [MGI Ref ID J:92429]

Blednov YA; Bergeson SE; Walker D; Ferreira VM; Kuziel WA; Harris RA. 2005. Perturbation of chemokine networks by gene deletion alters the reinforcing actions of ethanol. Behav Brain Res 165(1):110-25. [PubMed: 16105698]  [MGI Ref ID J:102583]

Brito BE; O'Rourke LM; Pan Y; Huang X; Park JM; Zamora D; Cook DN; Planck SR; Rosenbaum JT. 1999. Murine endotoxin-induced uveitis, but not immune complex-induced uveitis, is dependent on the IL-8 receptor homolog. Curr Eye Res 19(1):76-85. [PubMed: 10415460]  [MGI Ref ID J:56314]

Cameron MJ; Arreaza GA; Grattan M; Meagher C; Sharif S; Burdick MD; Strieter RM; Cook DN; Delovitch TL. 2000. Differential expression of CC chemokines and the CCR5 receptor in the pancreas is associated with progression to type I diabetes. J Immunol 165(2):1102-10. [PubMed: 10878389]  [MGI Ref ID J:120456]

Chantakru S; Kuziel WA; Maeda N; Croy BA. 2001. A study on the density and distribution of uterine natural killer cells at mid pregnancy in mice genetically-ablated for CCR2, CCR 5 and the CCR5 receptor ligand, MIP-1alpha J Reprod Immunol 49(1):33-47. [PubMed: 11137111]  [MGI Ref ID J:66438]

Crow AR; Song S; Semple JW; Freedman J; Lazarus AH. 2007. A role for IL-1 receptor antagonist or other cytokines in the acute therapeutic effects of IVIg? Blood 109(1):155-8. [PubMed: 16954498]  [MGI Ref ID J:142178]

Delogu A; Schebesta A; Sun Q; Aschenbrenner K; Perlot T; Busslinger M. 2006. Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells. Immunity 24(3):269-81. [PubMed: 16546096]  [MGI Ref ID J:113322]

Domachowske JB; Bonville CA; Gao JL; Murphy PM; Easton AJ; Rosenberg HF. 2000. The chemokine macrophage-inflammatory protein-1 alpha and its receptor CCR1 control pulmonary inflammation and antiviral host defense in paramyxovirus infection. J Immunol 165(5):2677-82. [PubMed: 10946298]  [MGI Ref ID J:120155]

Hamrah P; Yamagami S; Liu Y; Zhang Q; Vora SS; Lu B; Gerard CJ; Dana MR. 2007. Deletion of the chemokine receptor CCR1 prolongs corneal allograft survival. Invest Ophthalmol Vis Sci 48(3):1228-36. [PubMed: 17325167]  [MGI Ref ID J:123260]

Hsieh CH; Frink M; Hsieh YC; Kan WH; Hsu JT; Schwacha MG; Choudhry MA; Chaudry IH. 2008. The role of MIP-1 alpha in the development of systemic inflammatory response and organ injury following trauma hemorrhage. J Immunol 181(4):2806-12. [PubMed: 18684972]  [MGI Ref ID J:140173]

Ishida Y; Kimura A; Kondo T; Hayashi T; Ueno M; Takakura N; Matsushima K; Mukaida N. 2007. Essential Roles of the CC Chemokine Ligand 3-CC Chemokine Receptor 5 Axis in Bleomycin-Induced Pulmonary Fibrosis through Regulation of Macrophage and Fibrocyte Infiltration. Am J Pathol 170(3):843-54. [PubMed: 17322370]  [MGI Ref ID J:118647]

Lindell DM; Standiford TJ; Mancuso P; Leshen ZJ; Huffnagle GB. 2001. Macrophage Inflammatory Protein 1alpha/CCL3 Is Required for Clearance of an Acute Klebsiella pneumoniae Pulmonary Infection. Infect Immun 69(10):6364-9. [PubMed: 11553580]  [MGI Ref ID J:71659]

Low QE; Drugea IA; Duffner LA; Quinn DG; Cook DN; Rollins BJ; Kovacs EJ; DiPietro LA. 2001. Wound healing in MIP-1alpha(-/-) and MCP-1(-/-) mice. Am J Pathol 159(2):457-63. [PubMed: 11485904]  [MGI Ref ID J:70862]

Lu P; Li L; Wu Y; Mukaida N; Zhang X. 2008. Essential contribution of CCL3 to alkali-induced corneal neovascularization by regulating vascular endothelial growth factor production by macrophages. Mol Vis 14:1614-22. [PubMed: 18776949]  [MGI Ref ID J:140117]

Mahesh J; Daly J; Cheadle WG; Kotwal GJ. 1999. Elucidation of the early events contributing to zymosan-induced multiple organ dysfunction syndrome using MIP-1alpha, C3 knockout, and C5-deficient mice. Shock 12(5):340-9. [PubMed: 10565608]  [MGI Ref ID J:59655]

McMahon EJ; Cook DN; Suzuki K; Matsushima GK. 2001. Absence of macrophage-inflammatory protein-1alpha delays central nervous system demyelination in the presence of an intact blood-brain barrier. J Immunol 167(5):2964-71. [PubMed: 11509646]  [MGI Ref ID J:118563]

Miller CG; Cook DN; Kotwal GJ. 1996. Two chemotactic factors, C5a and MIP-1alpha, dramatically alter the mortality from zymosan-induced multiple organ dysfunction syndrome (MODS): C5a contributes to MODS while MIP-1alpha has a protective role. Mol Immunol 33(14):1135-7. [PubMed: 9047380]  [MGI Ref ID J:38592]

Miyazaki D; Nakamura T; Toda M; Cheung-Chau KW; Richardson RM; Ono SJ. 2005. Macrophage inflammatory protein-1alpha as a costimulatory signal for mast cell-mediated immediate hypersensitivity reactions. J Clin Invest 115(2):434-42. [PubMed: 15650768]  [MGI Ref ID J:96185]

Morteau O; Castagliuolo I; Mykoniatis A; Zacks J; Wlk M; Lu B; Pothoulakis C; Gerard NP; Gerard C. 2002. Genetic deficiency in the chemokine receptor CCR1 protects against acute Clostridium difficile toxin A enteritis in mice. Gastroenterology 122(3):725-33. [PubMed: 11875005]  [MGI Ref ID J:107677]

Narni-Mancinelli E; Campisi L; Bassand D; Cazareth J; Gounon P; Glaichenhaus N; Lauvau G. 2007. Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes. J Exp Med 204(9):2075-87. [PubMed: 17698589]  [MGI Ref ID J:126089]

Olszewski MA; Huffnagle GB; McDonald RA; Lindell DM; Moore BB; Cook DN; Toews GB. 2000. The role of macrophage inflammatory protein-1 alpha/CCL3 in regulation of T cell-mediated immunity to Cryptococcus neoformans infection. J Immunol 165(11):6429-36. [PubMed: 11086082]  [MGI Ref ID J:118399]

Olszewski MA; Huffnagle GB; Traynor TR; McDonald RA; Cook DN; Toews GB. 2001. Regulatory Effects of Macrophage Inflammatory Protein 1alpha/CCL3 on the Development of Immunity to Cryptococcus neoformans Depend on Expression of Early Inflammatory Cytokines. Infect Immun 69(10):6256-63. [PubMed: 11553568]  [MGI Ref ID J:71647]

Ramos CD; Canetti C; Souto JT; Silva JS; Hogaboam CM; Ferreira SH; Cunha FQ. 2005. MIP-1{alpha}[CCL3] acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential release of TNF-{alpha} and LTB4. J Leukoc Biol 78(1):167-77. [PubMed: 15831559]  [MGI Ref ID J:99288]

Ramos CD; Fernandes KS; Canetti C; Teixeira MM; Silva JS; Cunha FQ. 2006. Neutrophil recruitment in immunized mice depends on MIP-2 inducing the sequential release of MIP-1alpha, TNF-alpha and LTB(4). Eur J Immunol 36(8):2025-34. [PubMed: 16856209]  [MGI Ref ID J:116027]

Salazar-Mather TP; Hamilton TA; Biron CA. 2000. A chemokine-to-cytokine-to-chemokine cascade critical in antiviral defense. J Clin Invest 105(7):985-93. [PubMed: 10749577]  [MGI Ref ID J:120540]

Sato N; Ahuja SK; Quinones M; Kostecki V; Reddick RL; Melby PC; Kuziel WA; Ahuja SS. 2000. CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation. J Exp Med 192(2):205-18. [PubMed: 10899907]  [MGI Ref ID J:63491]

Sato N; Kuziel WA; Melby PC; Reddick RL; Kostecki V; Zhao W; Maeda N; Ahuja SK; Ahuja SS. 1999. Defects in the generation of IFN-gamma are overcome to control infection with Leishmania donovani in CC chemokine receptor (CCR) 5-, macrophage inflammatory protein-1 alpha-, or CCR2-deficient mice. J Immunol 163(10):5519-25. [PubMed: 10553079]  [MGI Ref ID J:91256]

Serody JS; Burkett SE; Panoskaltsis-Mortari A; Ng-Cashin J; McMahon E; Matsushima GK; Lira SA; Cook DN; Blazar BR. 2000. T-lymphocyte production of macrophage inflammatory protein-1alpha is critical to the recruitment of CD8(+) T cells to the liver, lung, and spleen during graft-versus-host disease Blood 96(9):2973-80. [PubMed: 11049973]  [MGI Ref ID J:65501]

Serody JS; Cook DN; Kirby SL; Reap E; Shea TC; Frelinger JA. 1999. Murine T lymphocytes incapable of producing macrophage inhibitory protein-1 are impaired in causing graft-versus-host disease across a class I but not class II major histocompatibility complex barrier. Blood 93(1):43-50. [PubMed: 9864144]  [MGI Ref ID J:51842]

Souza AL; Roffe E; Pinho V; Souza DG; Silva AF; Russo RC; Guabiraba R; Pereira CA; Carvalho FM; Barsante MM; Correa-Oliveira R; Fraga LA; Negrao-Correa D; Teixeira MM. 2005. Potential role of the chemokine macrophage inflammatory protein 1alpha in human and experimental schistosomiasis. Infect Immun 73(4):2515-23. [PubMed: 15784598]  [MGI Ref ID J:97199]

Trifilo MJ; Bergmann CC; Kuziel WA; Lane TE. 2003. CC chemokine ligand 3 (CCL3) regulates CD8(+)-T-cell effector function and migration following viral infection. J Virol 77(7):4004-14. [PubMed: 12634360]  [MGI Ref ID J:124745]

Van de Walle GR; Sakamoto K; Osterrieder N. 2008. CCL3 and viral chemokine-binding protein gg modulate pulmonary inflammation and virus replication during equine herpesvirus 1 infection. J Virol 82(4):1714-22. [PubMed: 18077722]  [MGI Ref ID J:141531]

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]

Wu Y; Li YY; Matsushima K; Baba T; Mukaida N. 2008. CCL3-CCR5 axis regulates intratumoral accumulation of leukocytes and fibroblasts and promotes angiogenesis in murine lung metastasis process. J Immunol 181(9):6384-93. [PubMed: 18941229]  [MGI Ref ID J:140725]

Wu YP; Proia RL. 2004. Deletion of macrophage-inflammatory protein 1 alpha retards neurodegeneration in Sandhoff disease mice. Proc Natl Acad Sci U S A 101(22):8425-30. [PubMed: 15155903]  [MGI Ref ID J:90687]

Yamagami S; Hamrah P; Miyamoto K; Miyazaki D; Dekaris I; Dawson T; Lu B; Gerard C; Dana MR. 2005. CCR5 chemokine receptor mediates recruitment of MHC class II-positive Langerhans cells in the mouse corneal epithelium. Invest Ophthalmol Vis Sci 46(4):1201-7. [PubMed: 15790880]  [MGI Ref ID J:104985]

Yanaba K; Mukaida N; Matsushima K; Murphy PM; Takehara K; Sato S. 2004. Role of C-C chemokine receptors 1 and 5 and CCL3/macrophage inflammatory protein-1alpha in the cutaneous Arthus reaction: possible attenuation of their inhibitory effects by compensatory chemokine production. Eur J Immunol 34(12):3553-61. [PubMed: 15517609]  [MGI Ref ID J:94599]

Yang X; Lu P; Fujii C; Nakamoto Y; Gao JL; Kaneko S; Murphy PM; Mukaida N. 2006. Essential contribution of a chemokine, CCL3, and its receptor, CCR1, to hepatocellular carcinoma progression. Int J Cancer 118(8):1869-76. [PubMed: 16284949]  [MGI Ref ID J:106825]

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

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

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 ~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.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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

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

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

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

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