These C5ar1 knock-out mice exhibit resistance to dermal infection. They are suitable for use in applications related to lung-associated diseases, immune complex associated injury, and complement innate immunity.
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 gene product is detected in bone marrow. 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, 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 compared to wild type. On a BALB/c background, these 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 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. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were backcrossed to C57BL/6 females. Heterozygotes were next mated to C57BL/6 mice for an unknown number of generations prior to arrival at The Jackson Laboratory. Once arrived, mice were crossed at least once to BALB/cJ. The resulting heterozygous mice were then intercrossed to generate homozygous mice.
|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 are maintained as heterozygotes or 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 #005676 in your Materials and Methods section.
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