These transgenic mice overexpress the secreted mouse <i>Il1rn</i> under the control of endogenous regulatory elements. The transgene contains the sequence encoding the secreted protein with a point mutation (G to A) in exon 3. These mice have an estimated 8 copies of the transgene in tandem array. Northern blot analysis of liver tissue following lipopolysaccharide (LPS) endotoxin challenge detects overexpression. RT-PCR analysis of corneal tissue detects higher levels of gene product (mRNA) than wildtype controls. The Donating Investigator reports that hemizygous mice are viable and fertile, whereas homozygous mice are sickly and die prematurely. Transgenic mice are less susceptible to LPS challenge than wildtype controls, but are more susceptible to experimental Listeria monocytogenes infection. Following endotoxin (LPS) challenge serum IL-1 levels are higher. Mice hemizygous for the transgene exhibit an intermediate susceptibility. Severity of stromal keratitis caused by herpes simplex virus (HSV) ocular infection is diminished. Mice with HSV ocular infection display reduced angiogenesis in the cornea, reduced polymorphonuclear leukocyte infiltration, decreased levels of macrophage-inflammatory protein 2 (MIP-2), IL-6, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2)levels, and delayed viral clearance. This mutant mouse strain may be useful in studies of inflammation and cytokine regulation.

These IL-Ira-Overexpressing mice express a transgene containing the sequence encoding the secreted mouse <i>Il1rn</i> protein with a point mutation (G to A) in exon 3, resulting in overexpression after lipopolysaccharide (LPS) endotoxin challenge.

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