B6.Cg-Tg(Il1rn)1Dih/J

Stock number: 004753
Product name: IL-Ira-Overexpressing
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

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

Detailed description

These transgenic mice overexpress the secreted mouse Il1rn 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.

Development

A transgenic construct containing the sequence encoding the mouse Il1rn gene (secreted protein) with a site directed mutation (G to A) in exon 3 was injected into fertilized B6CBAF2 eggs. The resulting transgenic mice, founder line 14, were backcrossed to the B6CBAF1/J background for an unspecified number of generations before being backcrossed for more than 20 generations onto the C57BL/6J background.

Allele

Symbol: Tg(Il1rn)1Dih
Name: transgene insertion 1, David Hirsh
MGI accession ID: MGI:3573755
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: IL1ra Tg; IL-1ra^tg
Marker symbol: Tg(Il1rn)1Dih
Marker name: transgene insertion 1, David Hirsh
Chromosome: UN
Strain of origin: (C57BL/6J x CBA)F2
Expressed genes: Il1rn,interleukin 1 receptor antagonist,mouse, laboratory
Molecular note: This transgene contains the sequence encoding the secreted gene protein and approximately 2.0kb of upstream and 2.5kb of downstream untranslated flanking regions, and a site directed mutation (G to A) in exon 3. Northern blot analysis of liver tissue following LPS challenge detects overexpression. Two lines were created and called T14 and T16.