B6N.129S1(FVB)-Ccl2^tm1.2Tyos/J

Stock number: 023347
Product name: MCP-1^flox
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These MCP-1^flox mice may be useful for generating tissue specific MCP-1 deficient mice for studying its role in the progression of specific inflammatory diseases.

Detailed description

These MCP-1^flox mice possess loxP sites flanking exons 1-2 of the chemokine (C-C motif) ligand 2 (Ccl2) gene. MCP-1 (monocyte chemoattractant protein-1) is a chemotactic factor that recruits monocytes and basophils to sites of inflammation or injury. This chemokine plays a role in the development of inflammatory responses as well as some diseases including atherosclerosis, psoriasis, pulmonary fibrosis, nephritis, multiple sclerosis and cancer. Mice that are homozygous for this allele are viable and fertile. These mice produce MCP-1 whose level is compatible to that in WT mice in response to intraperitoneal injection of thioglycollate or zymosan. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 1-2 deleted in cre-expressing tissues.

For example, when crossed to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003724) this mutant strain does not produce MCP-1 in response to peritonitis induction, but produces higher levels of MPC-3 and MCP-5. The number of macrophages recruited to the site of infection is reduced.

Development

A targeting vector was designed to insert a single loxP site upstream of exon 1, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 2, of the chemokine (C-C motif) ligand 2 (Ccl2) gene. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred with B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003724) to remove the neo cassette. Resulting offspring contained multiple gene rearrangments; intact floxed-exons 1-2, intact floxed-neo cassette, or excision of both exons 1-2 and the neo cassette. Progeny, containing only the floxed-exons 1-2, were crossed to remove the cre-expressing transgene. Resulting offspring were bred to C57BL/NCrl mice for at least 10 generations. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Ccl2^tm1.2Tyos
Name: targeted mutation 1.2, Teizo Yoshimura
MGI accession ID: MGI:5507824
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Ccl2
Marker name: chemokine (C-C motif) ligand 2
Chromosome: 11
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: Mice containing the floxed Ccl2^tm1Tyos allele were crossed with EIIa-Cre mice to remove the floxed neo cassette. These mice retain exons 1 and 2 flanked by loxP sites.