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)   01-MAR-06 Species laboratory mouse Generation N9+N2F13 (24-MAR-11) Generation Definitions   Donating Investigator Theodore M Danoff,   University of Pennsylvania

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by Northern blot analysis of lipopolysaccharide (LPS) stimulated peritoneal exudates cells. Homozygous mice have a reduced number of CD44 high CD4+ splenic T-cells. Delayed-type hypersensitivity (DTH) response (swelling) is impaired in homozygous mice sensitized with subcutaneous injection of keyhole limpet hemocyanin or bovine purified protein derivative. Immunohistochemical analysis of the DTH treated footpads reveals that the numbers of infiltrating macrophages is decreased, while infiltrating CD4+ and CD8+ T cells numbers remain unchanged. In vitro T cell proliferation, IFN-gamma and IL2 production is diminished. This mutant mouse strain may be useful in studies of delayed-type hypersensitivity and inflammatory responses.

Development
A targeting vector containing a hygromycin resistance gene driven by the phosphoglycerate kinase promoter and a diphtheria toxin gene was used to disrupt 334 bp of sequence in exon I. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 9 generations (June 2004).

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Ccl5^tm1Hso/Ccl5^tm1Hso

        involves: 129P2/OlaHsd * C57BL/6

• immune system phenotype
• decreased CD4-positive T cell number
  • percentage of CD44 high and CD62L low CD4+ cells is decreased by 24% and 14%, respectively, in the spleen   (MGI Ref ID J:75842)
• decreased T cell proliferation
  • polyclonal T cell proliferation (anti-CD3 mAb-induced) and antigen-specific T cell proliferation (KLH-induced) are reduced   (MGI Ref ID J:75842)
  • anti-CD3 mAb-induced lymph node T cell proliferation from unprimed mice is also reduced   (MGI Ref ID J:75842)
  • T cells from draining lymph nodes of KLH-immunized mice mixed with irradiated splenocytes (source of APCs) show a reduced proliferative capacity   (MGI Ref ID J:75842)
• decreased interferon-gamma secretion
  • T cells from KLH-immunized mice show a 76% reduction in IFN-gamma production when stimulated with anti-CD3 mAb and a 49% reduction when stimulated with KLH   (MGI Ref ID J:75842)
• decreased interleukin-2 secretion
  • T cells from KLH-immunized mice show a reduction in IL-2 production when stimulated with anti-CD3 mAb   (MGI Ref ID J:75842)
• decreased susceptibility to type IV hypersensitivity reaction
  • mutants show reduced delayed-type hypersensitivity response, with reduced KLH-specific swelling in both the ears and footpads, much milder dermal edema and inflammatory infiltrates than wild-type, and significant reduction in macrophage accumulation in footpads   (MGI Ref ID J:75842)
• hematopoietic system phenotype
• decreased CD4-positive T cell number
  • percentage of CD44 high and CD62L low CD4+ cells is decreased by 24% and 14%, respectively, in the spleen   (MGI Ref ID J:75842)
• decreased T cell proliferation
  • polyclonal T cell proliferation (anti-CD3 mAb-induced) and antigen-specific T cell proliferation (KLH-induced) are reduced   (MGI Ref ID J:75842)
  • anti-CD3 mAb-induced lymph node T cell proliferation from unprimed mice is also reduced   (MGI Ref ID J:75842)
  • T cells from draining lymph nodes of KLH-immunized mice mixed with irradiated splenocytes (source of APCs) show a reduced proliferative capacity   (MGI Ref ID J:75842)
• cellular phenotype
• decreased T cell proliferation
  • polyclonal T cell proliferation (anti-CD3 mAb-induced) and antigen-specific T cell proliferation (KLH-induced) are reduced   (MGI Ref ID J:75842)
  • anti-CD3 mAb-induced lymph node T cell proliferation from unprimed mice is also reduced   (MGI Ref ID J:75842)
  • T cells from draining lymph nodes of KLH-immunized mice mixed with irradiated splenocytes (source of APCs) show a reduced proliferative capacity   (MGI Ref ID J:75842)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      specific T cell deficiency
Immunodeficiency Associated with Other Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ccl5tm1Hso
Allele Name		targeted mutation 1, Hiroshi Sato
Allele Type		Targeted (knock-out)
Common Name(s)		CCL5-KO; RANTES-;
Mutation Made By		Donald Cook,   NIH/NIEHS
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Ccl5, chemokine (C-C motif) ligand 5
Chromosome		11
Gene Common Name(s)		D17S136E; MuRantes; RANTES; SCYA5; SISd; Scya5; TCP228; small inducible cytokine A5;
Molecular Note		A 333 bp region of the gene containing the promoter, transcription and translation initiation sites, and part of exon 1 was replaced with a PGK-hygro cassette via homologous recombination. Northern blot analysis confirmed the absence of gene expression in homozygous mutant mice. [MGI Ref ID J:75842]

Genotyping

Genotyping Information

Genotyping Protocols

Ccl5^tm1Hso, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Makino Y; Cook DN; Smithies O; Hwang OY; Neilson EG; Turka LA; Sato H; Wells AD; Danoff TM. 2002. Impaired T cell function in RANTES-deficient mice. Clin Immunol 102(3):302-9. [PubMed: 11890717]  [MGI Ref ID J:75842]

Additional References

Ccl5^tm1Hso related

Berres ML; Koenen RR; Rueland A; Zaldivar MM; Heinrichs D; Sahin H; Schmitz P; Streetz KL; Berg T; Gassler N; Weiskirchen R; Proudfoot A; Weber C; Trautwein C; Wasmuth HE. 2010. Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice. J Clin Invest 120(11):4129-40. [PubMed: 20978355]  [MGI Ref ID J:166910]

Crawford A; Angelosanto JM; Nadwodny KL; Blackburn SD; Wherry EJ. 2011. A role for the chemokine RANTES in regulating CD8 T cell responses during chronic viral infection. PLoS Pathog 7(7):e1002098. [PubMed: 21814510]  [MGI Ref ID J:183343]

Ergen AV; Boles NC; Goodell MA. 2012. Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing. Blood 119(11):2500-9. [PubMed: 22289892]  [MGI Ref ID J:182532]

Grayson MH; Ramos MS; Rohlfing MM; Kitchens R; Wang HD; Gould A; Agapov E; Holtzman MJ. 2007. Controls for lung dendritic cell maturation and migration during respiratory viral infection. J Immunol 179(3):1438-48. [PubMed: 17641009]  [MGI Ref ID J:149953]

Gregoire C; Cognet C; Chasson L; Coupet CA; Dalod M; Reboldi A; Marvel J; Sallusto F; Vivier E; Walzer T. 2008. Intrasplenic trafficking of natural killer cells is redirected by chemokines upon inflammation. Eur J Immunol 38(8):2076-84. [PubMed: 18624307]  [MGI Ref ID J:138561]

Henao-Mejia J; Elinav E; Jin C; Hao L; Mehal WZ; Strowig T; Thaiss CA; Kau AL; Eisenbarth SC; Jurczak MJ; Camporez JP; Shulman GI; Gordon JI; Hoffman HM; Flavell RA. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482(7384):179-85. [PubMed: 22297845]  [MGI Ref ID J:181354]

Hildebrandt GC; Olkiewicz KM; Choi S; Corrion LA; Clouthier SG; Liu C; Serody JS; Cooke KR. 2005. Donor T-cell production of RANTES significantly contributes to the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Blood 105(6):2249-57. [PubMed: 15546955]  [MGI Ref ID J:98128]

Kang SJ; Liang HE; Reizis B; Locksley RM. 2008. Regulation of hierarchical clustering and activation of innate immune cells by dendritic cells. Immunity 29(5):819-33. [PubMed: 19006696]  [MGI Ref ID J:142395]

Kovacic JC; Gupta R; Lee AC; Ma M; Fang F; Tolbert CN; Walts AD; Beltran LE; San H; Chen G; St Hilaire C; Boehm M. 2010. Stat3-dependent acute Rantes production in vascular smooth muscle cells modulates inflammation following arterial injury in mice. J Clin Invest 120(1):303-14. [PubMed: 20038813]  [MGI Ref ID J:156693]

Nesbeth YC; Martinez DG; Toraya S; Scarlett UK; Cubillos-Ruiz JR; Rutkowski MR; Conejo-Garcia JR. 2010. CD4+ T cells elicit host immune responses to MHC class II- ovarian cancer through CCL5 secretion and CD40-mediated licensing of dendritic cells. J Immunol 184(10):5654-62. [PubMed: 20400704]  [MGI Ref ID J:160992]

Tsukahara T; Makino Y; Fujii T; Ogawa M; Saisho H; Hamano Y; Ueda S; Akikusa B; Danoff TM. 2002. Role of RANTES in the development of autoimmune tissue injuries in MRL-Fas lpr mice. Clin Immunol 103(1):89-97. [PubMed: 11987989]  [MGI Ref ID J:76389]

Tyner JW; Uchida O; Kajiwara N; Kim EY; Patel AC; O'Sullivan MP; Walter MJ; Schwendener RA; Cook DN; Danoff TM; Holtzman MJ. 2005. CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Nat Med 11(11):1180-7. [PubMed: 16208318]  [MGI Ref ID J:102878]

Wareing MD; Lyon AB; Lu B; Gerard C; Sarawar SR. 2004. Chemokine expression during the development and resolution of a pulmonary leukocyte response to influenza A virus infection in mice. J Leukoc Biol 76(4):886-95. [PubMed: 15240757]  [MGI Ref ID J:92938]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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