Description

Strain Information

Former Names B6.Cg-Ccl2tm2.1Pame/J    (Changed: 26-JUL-11 ) 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 Heterozygote x Heterozygote         (Female x Male)   14-SEP-12 Species laboratory mouse Generation N10pN1 (19-OCT-12) Generation Definitions   Donating Investigator Eric G Pamer,   Memorial Sloan-Kettering Cancer Center

Description
These Ccl2-RFP^lox/lox mice contain loxP sites flanking exons 2-3 of the chemokine (C-C motif) ligand 2 (Ccl2 or Mcp1) gene, as well as an HA peptide followed by an aphthovirus 2A cleavage site and a cleavable red fluorescent protein (mcherry) at the 3' end of exon 3. Homozygous mice are viable and fertile. MCP1 is a chemokine required for the movement of monocytes from bone marrow into the blood stream during their recruitment to sites of injury and infection. Fluorescence is seen in all MCP1 expressing cells. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 2-3, as well as RFP expression, deleted in the cre-expressing tissue. Deletion of MCP1 results in decreased monocyte emigration from the bone marrow upon LPS stimulation and increased susceptibility to infection. These mice may be useful for studying emigration of inflammatory monocytes from the bone marrow after infection.

When bred to mice carrying Tg(Tek-cre)12Flv (Stock No. 004128) and induced by LPS or bacterial infection, Cre recombinase expression in endothelial cells results in abnormal monocyte migration.

When bred to mice carrying Tg(Nes-cre)1Kln (Stock No. 003771) and induced by LPS or bacterial infection, Cre recombinase expression in the nervous system results in abnormal monocyte migration.

Development
A targeting vector was designed to insert a loxP site upstream of exon 2 and a second loxP site downstream of exon 3 of the chemokine (C-C motif) ligand 2 (Ccl2 or Mcp1) gene. The targeting vector also inserted an HA peptide followed by an aphthovirus 2A cleavage site, a cleavable red fluorescent protein (mcherry), and a frt-flanked neomycin (neo) resistance cassette at the 3' end of exon 3. The construct was electroporated into B6(Cg)-Tyr^c-2J/J derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6J mice. Offspring, heterozygous for this Ccl2 allele, were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 005703) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene, resulting in a colony homozygous for the Ccl2-RFP^lox/lox allele. These mice were backcrossed to C57BL/6J mice for at least 10 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ccl2

004434	B6.129S4-Ccl2tm1Rol/J
014095	B6.Cg-Tg(GFAP-Ccl2)JE95Rmra/J

View Strains carrying other alleles of Ccl2     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Chemokine, Cc Motif, Ligand 2; CCL2   (CCL2) Human Immunodeficiency Virus Type 1, Susceptibility to   (CCL2) Mycobacterium Tuberculosis, Susceptibility to   (CCL2) Neural Tube Defects   (CCL2)

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.

Ccl2^tm1.1Pame/Ccl2^tm1.1Pame Tg(Alb-cre)21Mgn/0

        involves: C57BL/6 * DBA   (conditional)

• immune system phenotype
• *normal* immune system phenotype
  • LPS-induced monocyte emigration is normal   (MGI Ref ID J:171379)

Ccl2^tm1.1Pame/Ccl2^tm1.1Pame Tg(Nes-cre)1Kln/0

        involves: C57BL/6 * SJL   (conditional)

• immune system phenotype
• abnormal leukocyte migration
  • LPS-treated mice exhibit reduced percent of circulating Ly6C^hi monocyte compared with similarly treated wild-type mice   (MGI Ref ID J:171379)
  • mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice   (MGI Ref ID J:171379)
• increased susceptibility to bacterial infection
  • mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow and diminished bacterial clearance compared with similarly treated wild-type mice   (MGI Ref ID J:171379)
• cellular phenotype
• abnormal leukocyte migration
  • LPS-treated mice exhibit reduced percent of circulating Ly6C^hi monocyte compared with similarly treated wild-type mice   (MGI Ref ID J:171379)
  • mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice   (MGI Ref ID J:171379)

Ccl2^tm1.1Pame/Ccl2^tm1.1Pame Tg(Tek-cre)12Flv/0

        involves: C3H * C57BL/6   (conditional)

• immune system phenotype
• abnormal leukocyte migration
  • LPS-induced monocyte emigration is decreased compared to in similarly treated wild-type mice   (MGI Ref ID J:171379)
  • mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice   (MGI Ref ID J:171379)
• increased susceptibility to bacterial infection
  • mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice   (MGI Ref ID J:171379)
• cellular phenotype
• abnormal leukocyte migration
  • LPS-induced monocyte emigration is decreased compared to in similarly treated wild-type mice   (MGI Ref ID J:171379)
  • mice exposed to L. monocytogenes exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice   (MGI Ref ID J:171379)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Ccl2^tm1.1Pame/Ccl2^tm1.1Pame Lyz2^tm1(cre)Ifo/Lyz2⁺

        involves: 129P2/OlaHsd * C57BL/6   (conditional)

• immune system phenotype
• *normal* immune system phenotype
  • LPS-induced monocyte emigration is normal   (MGI Ref ID J:171379)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
Inflammation

Research Tools
Cre-lox System
      loxP-flanked Sequences
      loxP-flanked Sequences: Test/Reporter
Genetics Research
      Tissue/Cell Markers: Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ccl2tm1.1Pame
Allele Name		targeted mutation 1.1 Eric G Pamer
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Ccl2-RFPflox;
Strain of Origin		B6(Cg)-Tyr
Gene Symbol and Name		Ccl2, chemokine (C-C motif) ligand 2
Chromosome		11
Gene Common Name(s)		AI323594; CKb10; HC11; MCAF; MCP-1; MCP-4; MCP1; NCC-1; NCC1; SCYA13; SCYL1; SMC-CF; Scya2; Sigje; expressed sequence AI323594; monocyte chemoattractant protein-1; monocyte chemotactic protein; small inducible cytokine A2; small inducible gene JE;
Molecular Note		A loxP site was inserted upstream of exon 2. Exon 3 was replaced with a modified exon 3 with an HA-2A cleavable mCherry and 3' loxP site. A floxed neo cassette used for selection purposes was removed by cre-mediated recombination. [MGI Ref ID J:171379]
Gene Symbol and Name		Ccl2, chemokine (C-C motif) ligand 2
Chromosome		11
Gene Common Name(s)		AI323594; CKb10; HC11; MCAF; MCP-1; MCP-4; MCP1; NCC-1; NCC1; SCYA13; SCYL1; SMC-CF; Scya2; Sigje; expressed sequence AI323594; monocyte chemoattractant protein-1; monocyte chemotactic protein; small inducible cytokine A2; small inducible gene JE;

Genotyping

Genotyping Information

Genotyping Protocols

Ccl2^tm1.1Pamealternate1,

Separated MCA

Ccl2^tm1.1Pamealternate1, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Shi C; Jia T; Mendez-Ferrer S; Hohl TM; Serbina NV; Lipuma L; Leiner I; Li MO; Frenette PS; Pamer EG. 2011. Bone Marrow Mesenchymal Stem and Progenitor Cells Induce Monocyte Emigration in Response to Circulating Toll-like Receptor Ligands. Immunity 34(4):590-601. [PubMed: 21458307]  [MGI Ref ID J:171379]

Additional References

Ccl2^tm1.1Pame related

Tagliani E; Shi C; Nancy P; Tay CS; Pamer EG; Erlebacher A. 2011. Coordinate regulation of tissue macrophage and dendritic cell population dynamics by CSF-1. J Exp Med 208(9):1901-16. [PubMed: 21825019]  [MGI Ref ID J:177594]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Heterozygote x Heterozygote         (Female x Male)   14-SEP-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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