MCP-1-/- mice on FVB/NJ may be useful in studies related to leukocyte trafficking and diet-induced obesity.
E. Angela Murphy, University of South Carolina
MCP-1-/- mice have neomycin resistance and herpes simplex virus thymidine kinase genes disrupting exon 2 of the chemokine (C-C motif) ligand 2 (Ccl2) gene. An inframe stop codon was also inserted into exon 1. MCP-1 is a member of the C-C chemokine family that bind to G protein coupled receptors to regulate macrophage recruitment during wound healing, infection, and inflammation. Mice that are homozygous for the targeted mutation are viable and fertile. No gene product is detected in lipopolysaccharide (LPS) -stimulated peritoneal macrophages isolated from homozygous mice. The numbers of peritoneal macrophages, Kupffer cell and alveolar macrophages were similar to levels found in wildtype mice. Thioglycollate induced peritonitis results in impaired recruitment of monocytes and macrophages to peritoneal cavity. Cellular recruitment to delayed-type hypersensitivity challenges and secondary granulomata is reduced. However, on this FVB/NJ background, an increase in high fat diet (HFD)-related pathologies, including adiposity, metabolic dysfunction, macrophage number, macrophage markers, inflammatory cell infiltration, and fibrosis is seen following 16 weeks on a 40% HFD. Also, MCP-1 deletion results in decreased tumorigenesis, indicated by reduced primary tumor volume and multiplicity, and a delay in tumor progression.
Of note, this KO allele is also available on a C57BL/6J congenic background as Stock No. 004434.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 2 and insert an inframe stop codon into exon 1 of the chemokine (C-C motif) ligand 2 (Ccl2) gene. The construct was electroporated into 129S4/SvJae derived J1 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 ten generations. This strain arrived as Stock No. 004434. Some of these mice were further backcrossed to FVB/NJ mice (Stock No. 001800) for at least 8 generations by Dr. Angela Murphy (University of South Carolina). This FVB/NJ congenic line was sent back to The Jackson Laboratory by Dr. Murphy and is now available as this Stock No. 030109.
|Allele Name||targeted mutation 1, Barrett J Rollins|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||(MCP)1-; CCL2-; CCL2KO; MCP-1-; MCP-1KO; Scya2-|
|Gene Symbol and Name||Ccl2, chemokine (C-C motif) ligand 2|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A small deletion and an in frame stop codon were created in exon 1. A PGK-neomycin resistance cassette was also inserted into exon 2. Secreted protein was not detected in stimulated peritoneal macrophages from homozygous mutant mice.|
|Mutations Made By|| |
Barrett Rollins, Dana-Farber Cancer Inst, Harvard Med Sch
When maintaining a live colony, homozygous mice may be bred together.
When using the MCP-1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #030109 in your Materials and Methods section.
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