NOD.Cg-Il1r1^tm1Roml/HetJ

Stock number: 005078
Product name: IL-1RI^-
Research areas: Cancer Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These Il1r1 knock-out mice exhibit a reduced inflammatory response and no response to interleukin-1 alpha or beta.

Detailed description

Mice homozygous for the Il1r1^tm1Roml targeted mutation develop normally, exhibit a reduced inflammatory response and no response to interleukin-1 alpha or beta. Homozygous mice have a reduced acute phase and delayed type hypersensitivity response and are highly susceptible to Listeria monocytogenes infection. Equilibrium binding experiments using radiolabeled anti-mouse IL1R1 antibody, 35F5, show no detectable expression of IL1R1 protein in primary murine embryonic fibroblasts (Labow et al, 1997). NOD females homozygous for the Il1r1^tm1Roml mutation experience a slight, yet significant delay in diabetes development, with an overall incidence of 75% compared to 100% in wild types. There is no statistical difference between mutant and wild type NOD mice in diabetes development following cyclophosphamide treatment or in the rate at which they mediate autoimmune rejection of syngeneic fetal pancreatic grafts. Adoptive transfer of NOD.Cg-Tg(TcraBDC2.5)1DoiTg(TcrbBDC2.5)2Doi Prkdc ^scid spleen cells results in diabetes onset in irradiated NOD.Cg-Il1r1^tm1Roml recipients at 20 days post-transfer, compared to 11 days in wild type recipients. Introduction of the Il1r1^tm1Roml mutation does not alter the rate of diabetes development in NOD.Cg-Tg(8.3TCR) mice (Thomaset al, 2004). Islets isolated from Il1r1 homozygous mice are resistant to toxic effects of cytokines.

This mutant mouse strain may be useful in studies of the role of interleukin-1receptor type 1 in autoimmune diseases such as type 1 diabetes.

Development

A construct containing a neomycin expression cassette replacing approximately a 1 kb region, including the exon encoding the signal peptide and possibly containing an ATG initiation codon of Il1r1, rendering the sequence out of frame after the insertion, was transfected into W9.5 (129S1/SvImJ derived) ) embryonic stem cells (ES cells). ). These ES cells were injected into C57BL/6 blastocysts. To establish a colony and germ line transmission chimeric mice were backcrossed to C57BL/6 or 129/Sv and intercrossed to generate homozygotes (Labow et al, 1997). Thomas et al, 2004, subsequently backcrossed this mutation to NOD/LtJ for 10 generations prior to intercrossing to fix the mutation to homozygosity. A genome wide scan confirmed that all known Idd markers were homozygous for the NOD allele. In 2004, the Type 1 Diabetes Resource received NOD.Cg-Il1r1^tm1Roml/HetJ at generation N10F7.

Allele

Symbol: Il1r1^tm1Roml
Name: targeted mutation 1, Mark A Labow
MGI accession ID: MGI:1857441
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Il1r1
Marker name: interleukin 1 receptor, type I
Chromosome: 1
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: A neomycin resistance gene cassette replaced an ~1 kb region of the DNA that includes one exon of the gene, which encodes the signal peptide and contains a possible ATG initiation codon.