BXSB.129S2(B6)-Il6^tm1Kopf/DcrJ

Stock number: 021873
Product name: IL-6^-
Research areas: Cancer Research, Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Research Tools

Description

IL-6-deficient BXSB.Yaa mice (BXSB.IL6-/- or BXSB.Yaa Il6-/-) are a BXSB-congenic strain carrying a null mutation of the interleukin 6 gene. The immune response-deficiency of BXSB.IL6-/- mice significantly delays manifestation of the spontaneous lupus-like autoimmune syndrome observed for BXSB/MpJ inbred mice. These BXSB.IL6-/- mice may be useful in studying the function of IL-6-producing cells (macrophages, T helper 2 (Th2) cells, etc.) in autoimmune disease.

Detailed description

IL-6-deficient BXSB.Yaa mice (BXSB.IL6-/- or BXSB.Yaa Il6-/-) are a BXSB-congenic strain carrying a null mutation of the interleukin 6 gene. IL-6 has both pro-inflammatory and anti-inflammatory/regenerative cytokine function.

BXSB/MpJ inbred males (Stock No. 000740) develop a spontaneous lupus-like autoimmune syndrome: mortality starts at ~13 weeks of age with 50% lethality by ~30 weeks and 76% lethality by ~40 weeks. BXSB/MpJ inbred females develop a greatly attenuated form of autoimmune disease because they lack Yaa.

Homozygous (IL6-/-) mice are viable and fertile. Homozygotes exhibit impaired immune response to pathogens, decreased T cell numbers, resistance to plasma cell neoplasia, defective wound healing and defective liver regeneration. Compared to BXSB/MpJ, the immune response-deficiency of BXSB.IL6-/- mice significantly delays manifestation of the autoimmune phenotype in both males and females. Specifically, mortality in males is only 50% by ~45 weeks of age.

Heterozygous males (BXSB.IL6+/-) develop the BXSB/MpJ autoimmune phenotype. Heterozygous females develop a greatly attenuated form of autoimmune disease because they lack Yaa.

C57BL/6J-congenic mice harboring this IL-6 null allele are described and available from The Jackson Laboratory Repository as Stock No. 002650.

Development

The IL-6 null allele (Il6^tm1Kopf) was designed by Drs. Manfred Kopf and Georges Kohler (Max Planck Institut Fur Immunbiologie) to disrupt the first coding exon (exon 2) of the interleukin 6 gene on chromosome 5 with a neomycin resistance cassette. C57BL/6J-congenic mice harboring this IL-6 null allele are described and available from The Jackson Laboratory Repository as Stock No. 002650.
Dr. Derry C. Roopenian (The Jackson Laboratory) obtained some of these mutant mice and backcrossed them with BXSB/MpJ inbred mice (Stock No. 000740) for 11 generations, and then maintained the colony by breeding homozygous mice together. In 2013, Dr. Roopenian sent some BXSB.IL6-/- mice at generation N11F11 to The Jackson Laboratory Repository (Autoimmune Resource) to establish Stock No. 021873. Male mice have the BXSB/MpJ-derived Y chromosome that contains the Y-linked autoimmune accelerator locus (Yaa).

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.