NOD.129S2(B6)-Il6^tm1Kopf/YgchJ

Stock number: 029264
Product name: Il-6 KO
Research areas: Cancer Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These interleukin 6 (IL6) mutant mice develop spontaneous Type 1 diabetes similar to that of the NOD/ShiLtJ (Stock No. 001976) wild type mice. They may show defects in responses to various viruses and in inflammatory responses to tissue damage or infection.

Detailed description

Mice homozygous for the targeted mutation are viable and fertile. No gene product (mRNA) is detected by RT-PCR analysis of lipopolysaccharide (LPS) challenged macrophages. Bioassay and enzyme-linked immunosorbent assay (ELISA) analysis of serum from LPS-challenged homozygotes reveals no detectable protein activity. These interleukin 6 (IL6) mutant mice develop spontaneous Type 1 diabetes similar to that of the NOD/ShiLtJ (Stock No. 001976) wild type mice. They may also show defects in responses to various viruses and in inflammatory responses to tissue damage or infection.

Of note, IL6-mutant mice may be available on other genetic backgrounds including mixed B6;129S2 (Stock No. 002254), C57BL/6J (Stock No. 002650), and BALB/cByJ (Stock No. 007078).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these NODShiLt/J-congenic mice could vary from that originally described on a B6;129S2 genetic background. We may modify the strain description if necessary as published results become available.

Development

The interleukin 6 targeted mutation was created by Manfred Kopf and Georges Kohler (Max Planck Institut Fur Immunbiologie, Freiburg Germany). A targeting vector was designed to place a neomycin resistance cassette into the first coding exon (exon 2) of the targeted gene. This construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting mice were sent to The Jackson Laboratory where the mouse line was bred to C57BL/6J (Stock No. 000664) mice for 11 generations and were maintained as Stock No. 002650. Some of these mice were obtained by Dr. Sheela Ramanathan (University of Sherbrooke), who backcrossed them to NOD/ShiLtJ mice (Stock No. 001976) for 10 generations. These NOD congenic mice were further backcrossed to NOD/LtDvs mice for 3 generations by Dr. Yi-Guang Chen at Medical College of Wisconsin. Dr. Chen sent mice back to The Jackson Laboratory, where sperm was cryopreserved. An aliquot of frozen sperm was used to fertilize NOD/ShiLtJ oocytes to establish our live colony of this Stock No. 029264.

Allele

Symbol: Il6^tm1Kopf
Name: targeted mutation 1, Manfred Kopf
MGI accession ID: MGI:1857197
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Il6
Marker name: interleukin 6
Chromosome: 5
Strain of origin: 129S2/SvPas
Molecular note: A neomycin selection cassette was inserted into exon 2. RT-PCR experiments on RNA derived from LPS-stimulated macrophages of homozygous mice demonstrated that no detectable transcript was produced from this allele. ELISA and bioassay experiments confirmed that no functional protein was made in homozygous mice.