Mcp-2-/Mcp-5- mice have a floxed neomycin cassette disrupting expression of Ccl8 and Ccl12. Removal of the neo cassette restores expression of Ccl8. These mice may be useful for studying monocyte mobilization from bone marrow and recruitment to inflammatory sites.
Andrew D Luster, Massachusetts General Hospital-East
Mcp-2-/Mcp-5- mutant mice have a floxed neo cassette disrupting the coding region of the chemokine (C-C motif) ligand 12 (Ccl12 or Mcp-5) gene. The insertion of the neo cassette inhibits expression of MCP-5 and MCP-2 (chemokine (C-C motif) ligand 8 (Ccl8), which lies 12kb downstream of Mcp-5. Mice that are homozygous for this allele are viable and fertile. Ccl8 and Ccl12 are chemotactic factors that attract monocytes, lymphocytes, basophils and eosinophils to sites of injury or infection through association with CCR8 (chemokine (C-C motif) receptor 8) and CCR2, respectively. Mcp-2-/Mcp-5- mice are more susceptible to Listeria monocytogenes infection than wild-type mice. They have normal numbers of monocytes in bone marrow and in blood.
When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have the neo cassette removed and will have expression of MCP-2 restored in cre-expressing tissue (see Stock No. 029089).
A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette into exon 1 of the chemokine (C-C motif) ligand 12 (Ccl12) gene. The construct was electroporated into 129S4/SvJae-derived RF8 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6 mice for at least 10 generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
|Allele Name||targeted mutation 1, Israel F Charo|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Ccl8/Ccl12tm1Ifc; Mcp-2-/Mcp-5-|
|Gene Symbol and Name||Ccl12, chemokine (C-C motif) ligand 12|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A floxed neomycin resistance cassette was inserted into the chemokine (C-C motif) ligand 12 locus. This insertion disrupted the expression of this gene as well as chemokine (C-C motif) ligand 8.|
When maintaining a live colony homozygous mice may be bred together.
When using the Mcp-2-/Mcp-5- mouse strain in a publication, please cite the originating article(s) and include JAX stock #029088 in your Materials and Methods section.