Cxcr1 knock-out mice exhibit increased susceptibility to Pseudomonas aeruginosa and Candida albicans infection. This strain is useful in studies of immune responses to bacterial and fungal infection.
Philip M. Murphy, NIAID, NIH
The targeted Cxcr1 gene encodes a receptor for mouse chemokine Cxcl5/LIX. A genetic variant in this gene have been associated with susceptibility to bacterial infection of the kidney (pyelonephritis). These Cxcr1 knock-out mice carry an allele in which two thirds of the coding sequence has been replaced by a neo cassette. Mice that are homozygous for the targeted mutation are viable and fertile. Knock-out mice are more susceptible to systemic fungal (Candida albicans) infection, exhibiting increased mortality. Homozygous mice produce neutrophils that are defective in intracellular killing of bacteria and bacterial clearance in Pseudomonas aeruginosa infection. Extracellular bacterial killing is not altered. Bone marrow myeloid cells from homozygotes produce lower amounts of ROS (reactive oxygen species) than controls when stimulated with CXCL8 or bacterial flagellin.
A targeting vector containing an 1.7 kb neo cassette was used to replace 2.7 kb of sequence encoding two thirds of Cxcr1 coding sequence (codons 121 to 351) and 2028 bp of the 3’ UTR. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were bred to C57BL/6 wildtype mice to generate heterozygotes. The heterozygotes were intercrossed to generate homozygotes. The mice were then backcrossed to C57BL/6NTac for 10 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).
|Allele Name||targeted mutation 1, Ji-Liang Gao|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Cxcr1, chemokine (C-X-C motif) receptor 1|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A 1.7 kb neomycin resistance gene replaced 2.7 kb of the gene, which includes two thirds of the coding sequence. The deleted region starts from the middle of the third transmembrane segment predicted from the sequence (codons 121 to 351) plus 2028 base pairs of the 3' untranslated region.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Cxcr1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #032934 in your Materials and Methods section.