These Il1rn knock-out mice have decreased body mass compared with wild-type controls, and are more susceptible than controls to lethal endotoxemia. They are suitable for use in applications related to the study of inflammation and cytokine regulation.
Dr. Emmet Hirsch, Northwestern University
Mice that are homozygous for the targeted mutation are viable and do not display any gross physical or behavioral abnormalities. By 6 weeks of age homozygous mice have lower body weight. Homozygous females may have reduced litter sizes. No gene product (mRNA) is detected by Northern blot analysis of lung tissue after lipopolysaccharide (LPS) challenge. Mice homozygous for the mutation are less susceptible to experimental Listeria monocytogenes infection, but are more susceptible to LPS endotoxin challenge. After LPS challenge IL-1 levels are decreased. Basal serum amyloid protein and serum IL-6 levels are higher. Hepatic acute phase protein inflammatory response and mortality to subcutaneous turpentine abscess induction are increased. When fed a high fat diet containing cholate for 12 weeks, homozygotes exhibit a 3-fold decrease in total cholesterol (non-HDL). Heterozygotes fed the same diet exhibit an intermediate decrease in total cholesterol. Immunohistochemical analysis of homozygotes fed the high fat diet did not detect any gene product in the proximal aorta. This mutant mouse strain may be useful in studies of inflammation and cytokine regulation.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes and a site directed mutation (G to A) in exon 3 was used to disrupt exon 3, which encodes the secreted gene product (protein). The construct was electroporated into derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to the same for more than 25 generations.
|Allele Name||targeted mutation 1, David Hirsh|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||IL-1ra-; rako|
|Gene Symbol and Name||Il1rn, interleukin 1 receptor antagonist|
|Strain of Origin||129S/SvEv-Gpi1c|
|Molecular Note||Insertion of a neomycin resistance cassette into exon III disrupted the sequence encoding the secreted protein. Northern blot analysis of lung tissue collected after LPS injection did not detect transcript in homozygous mutant mice.|
When maintaining a live colony, these mice are bred as heterozygotes, due to the reduced fertility of homozygous females.
When using the IL-1ra KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004754 in your Materials and Methods section.
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