Deficiency of complement component 5a receptor 1 in these C5ar1tm1Cge knock-out mice affects a wide range of physiological responses, and has been implicated in autoimmune and inflammatory disorders.
Craig Gerard, Childrens' Hospital Boston, Harvard MS
Mice homozygous for the targeted mutation are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities when maintained under barrier conditions. No mRNA is detected by Northern blot analysis of bone marrow cells isolated from homozygotes, and neutrophils fail to respond to recombinant C5a in vitro. The immune response of homozygous mice following inoculation or challenge has been characterized on a C57BL/6 background in a number of studies. Following intratracheal inoculation, mutant mice have impaired bacterial clearance in the lungs, associated with extensive secondary infection, despite increased neutrophil accumulation. Conversely, homozygous mutants are protected against immune-complex-associated injury in the lung, peritoneum, skin, and kidney but not against experimental autoimmune encephalomyelitis. Induced acute pancreatitis and pancreatitis-associated lung injury is more severe in homozygotes compared to wildtype. On a BALB/c background, homozygous mutant mice are more resistant to dermal infection, and lymph node cells have greatly increased antigen recall, as measured by interferon gamma secretion, compared to wild type. Homozygotes fail to develop airway hyper-reactivity in hapten asthma models (background not-identified). This mutant can be used to study many lung-associated diseases, immune complex associated injury, and complement-mediated innate immunity.
A targeting vector containing a mouse phosphoglycerate kinase promoter-driven neomycin resistance gene was used to replace the entire coding region of the endogenous gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells, and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were crossed to C57BL/6 females. Heterozygotes were mated to C57BL/6 mice for 2 generations and then backcrossed 10 generations to BALB/c before being made homozygous. Upon arrival at The Jackson Laboratory, homozygous mice were bred at least one generation to BALB/cJ (Stock No. 000651).
|Allele Name||targeted mutation 1, Craig Gerard|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||C5aR-; C5aRKO|
|Gene Symbol and Name||C5ar1, complement component 5a receptor 1|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A PGK-neomycin resistance cassette replaced the entire coding region of the gene. Northern analysis of bone marrow cells did not detect expression in homozygous mutant mice.|
|Mutations Made By|| |
Craig Gerard, Childrens' Hospital Boston, Harvard MS
When maintaining a live colony, these mice may be bred as homozygotes. For homozygous colonies, SPF conditions are recommended as mutant mice have impaired clearance of bacterial infection.
When using the C5aR- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006845 in your Materials and Methods section.
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