B6.129S4-Ccr2^tm1Ifc/J

Stock number: 004999
Product name: CCR2-
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Ccr2 deficient mice exhibit defective monocyte recruitment during immune responses.

Note, a similar KO/KI strain is also available that expresses EGFP from the Ccr locus (Stock No. 027619).

Detailed 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 CCR2 mRNA is detected by RT-PCR analysis of spleen or thioglycollate elicited peritoneal exudate cells.
    The absence of the CCR2 chemokine receptor in these mice affects monocyte/macrophage infiltration leading to inflammatory responses, which, in turn, impact various systematic processes including immune response to various pathogens, reduced retinal vascularation, aggravation of mnesic deficits, pathogenesis of angiotensin II-induced cardiac fibrosis, exacerbation of collagen-induced arthritis, and reduced hepatic steatosis in obese mice.
    Specific effects include defective delayed-type hypersensitivity and production of Th1-type cytokine immune responses. Mycobacteria bovis purified protein derivative induced lung granulomas are initially smaller in size and contain fewer macrophages than wild-type controls. Ccr2-KO mice are extremely susceptible to pulmonary infection with Burkholderia mallei compared with wild-type mice. Increased mortality due to West Nile virus infection is seen. Mutant mice also exhibit decreased interferon-alpha production after lung granuloma induction. When challenged with thioglycollate treatment homozygotes respond with reduced peritoneal macrophage recruitment. Macrophages derived from these animals fail to migrate in response monocyte chemoattractant protein-1. Homozygotes are resistant to experimental autoimmune encephalomyelitis, a macrophage-mediated inflammatory disease.

Development

A targeting vector containing polII- neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the entire coding region except the first 39 nucleotides and 5' untranslated region. The construct was electroporated into 129S4/SvJae derived RF8 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 for nine generations to C57BL/6 mice (October 2003).

Allele

Symbol: Ccr2^tm1Ifc
Name: targeted mutation 1, Israel F Charo
MGI accession ID: MGI:2158213
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ccr2
Marker name: chemokine (C-C motif) receptor 2
Chromosome: 9
Strain of origin: 129S4/SvJae
Molecular note: The coding region and 3' untranslated region are replaced with a polII-neo cassette. Absence of transcript was confirmed by RT-PCR using mRNA isolated from spleens and thioglycolate elicited peritoneal exudate cells of homozygous mutant animals.