Mice harboring this chemokine (C-X-C motif) receptor 2 (Cxcr2) "knockout" mutation may be useful in studying inflammation, immunology, cancer biology, demyelinating autoimmune disease (such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) protocols), and myelin repair.
Richard M Ransohoff, Cleveland Clinic
Homozygous mice are viable but fail to thrive (few pups are produced). Maintaining homozygous mice in a gnotobiotic vivarium may enhance strain breeding performance. Heterozygous mice are viable and fertile with no reported needs for special husbandry. The donating investigator reports that Cxcr2-deficient mice on the SJL/J genetic background are resistant to experimental autoimmune encephalomyelitis (EAE) protocols compared to susceptible SJL/J wildtype mice. Cxcr2-deficiency on other genetic backgrounds is associated with several abnormalities, including neurological defects, impaired wound healing, impaired angiogenesis, and altered growth of induced/implanted tumors. In addition, homozygotes may also exhibit splenomegaly, lymphadenopathy, and increased susceptibility to various pathogens due to impaired neutrophil recruitment and decreased pathogen clearance during innate immune responses. These mutant mice may be useful in studying inflammation, immunology, cancer biology, demyelinating autoimmune disease (such as multiple sclerosis and EAE protocols), and myelin repair.
There are reported differences for Cxcr2-deficient mice on different genetic backgrounds. On a C57BL/6 genetic background, Cxcr2-deficiency imparts resistance to cuprizone-induced demyelination compared to wildtype C57BL/6 mice. Only modest demyelination is observed independent of Cxcr2-deficiency on the cuprizone-resistant BALB/c genetic background. Similarly, BALB/c inbred mice are relatively resistant to experimental autoimmune encephalomyelitis (EAE), while Cxcr2-deficiency on EAE-susceptible C57BL/6 or (SWRxSJL)F1 genetic backgrounds result in decreased incidence, decreased mortality, and enhanced recovery. In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector was designed to replace the single exon of the targeted gene with a PGK-neomycin resistance cassette. The construct was electroporated into the 129S2/SvPas-derived D3 embryonic stem (ES) cells, and correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric males were bred to C57BL/6J females to establish a mutant colony, and then backcrossed to BALB/c for many generations in the laboratory of Dr. Mark Moore (Genentech, Inc, San Francisco). Mice on this BALB/c congenic background were sent to Jackson Laboratory Repository (as Stock No. 002724). These mice were then sent to Dr. Richard M. Ransohoff (Cleveland Clinic), where they were backcrossed to SJL/J inbred mice for at least 11 generations and then sent to The Jackson Laboratory Repository. Upon arrival, mice were bred with SJL/J inbred mice (Stock No. 000686) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Mark Moore|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Cmkartm1Mwm; Cmkar2tm1Mwm; CXCR-; CXCR2-; CXCR2 -; Il8rbtm1Mwm; mCXCR-; mCXCR2-; mIL-8Rh-; mIL-8Rh KO|
|Gene Symbol and Name||Cxcr2, chemokine (C-X-C motif) receptor 2|
|Strain of Origin||129S2/SvPas|
|Molecular Note||A neomycin selection cassette replaced the entire coding sequence of the gene.|
|Mutations Made By|| |
Dr. Mark Moore, Deltagen
When maintaining a live colony, heterozyous mice may be bred together, to wildtype mice from the colony, or to SJL/J inbred mice (Stock No. 000686). Homozygous mice are viable and fertile but fail to thrive (few pups are produced). The donating investigator reports that heterozygous (or homozygous) males may be aggressive. Maintaining homozygous mice in a gnotobiotic vivarium may enhance strain breeding performance.
When using the mIL-8Rh- mouse strain in a publication, please cite the originating article(s) and include JAX stock #013043 in your Materials and Methods section.