Mice homozygous for the knock-out of chemokine (C-C motif) receptor 3 (Ccr3tm1Cge) have impaired trafficking of eosinophils with a decrease in the number of eosinophils in the small intestine and an increase in the spleen. These mice may be useful in studies of atopic dermatitis, allergic asthma, increased airway responsiveness/airway hyperresponsiveness.
Craig Gerard, Childrens' Hospital Boston, Harvard MS
Mice homozygous for this CCR3 (chemokine (C-C motif) receptor 3) targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by RNA protection assay analysis of thymus, spleen and lung tissues. Mice homozygous for the mutation have impaired trafficking of eosinophils. A 7-fold decrease in the number of eosinophils in the small intestine and a 6-fold increase in the spleen is observed. Aerosol allergen challenge does not cause the expected infiltration of eosinophils to the lung tissue and airway lumens (50-70% reduction), although abundant eosinophils are found in the airway blood vessels. Concurrent increases in eosinophils in the spleen and intraepithelial mast cells in the spleen occur after allergen challenge. Homozygotes exhibit increased bronchoconstriction with allergen-induced airway hyperresponsiveness. There is no increase in eosinophils or eosinophil product major basic protein (MBP) in the skin after epicutaneous allergen treatment. Homozygous mice that have been epicutaneously sensitized do not develop increased airway responsiveness, or AHR, following inhalation challenge. These CCR3 mutant mice may be useful in studies of atopic dermatitis, allergic asthma, increased airway responsiveness/airway hyperresponsiveness (AHR).
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes driven by the phosphoglucokinase promoter was used to disrupt a 3kb region containing 39 bp of the region encoding the N-terminal, the start codon and a 5' untranslated region. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts. The resulting chimeric animals were crossed to BALB/c mice, and then backcrossed to the same for 13 generations.
|Allele Name||targeted mutation 1, Craig Gerard|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CCR3-; CCR3 KO|
|Gene Symbol and Name||Ccr3, chemokine (C-C motif) receptor 3|
|Strain of Origin||129S4/SvJae|
|Molecular Note||The gene was disrupted by replacement of a 3 kb region containing the start codon, 39 bp of the N-terminal coding region, and the 5' untranslated region with a PGK-neo cassette via homologous recombination. Absence of gene expression was confirmed by RT-PCR analysis of bone marrow mRNA from homozygous mutant animals.|
|Mutations Made By|| |
Craig Gerard, Childrens' Hospital Boston, Harvard MS
When maintaining a live colony, these mice are bred as homozygotes.
When using the C.129S4-Ccr3tm1Cge/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #005440 in your Materials and Methods section.
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