IL-10-deficient BXSB.Yaa mice (BXSB.IL10-/- or BXSB.Yaa Il10-/-) are a BXSB-congenic strain carrying a null mutation of the interleukin 10 gene. Homozygous deficiency of this anti-inflammatory cytokine results in enhanced T helper 1 (Th1) immune responses. BXSB.IL10-/- have an accelerated and more severe form of spontaneous lupus-like autoimmune syndrome compared to BXSB/MpJ inbred mice. These BXSB.IL10-/- mice may be useful in studying how IL-10-producing T helper 2 (Th2) cells normally attenuate spontaneous lupus-like autoimmune syndrome.
Dr. Derry Roopenian, The Jackson Laboratory
Mice homozygous for the Il10tm1Cgn targeted mutation are viable and fertile when housed under specific pathogen free (SPF) conditions. Homozygous deficiency of this anti-inflammatory cytokine results in enhanced T helper 1 (Th1) immune responses. Under conventional housing conditions, Il10-deficiency is associated with altered lymphocyte and myeloid profiles, elevated serum amyloid A levels, altered responses to inflammatory or autoimmune stimuli (both endogenous and induced), increased prevalence of colorectal adenocarcinoma (especially on 129/Sv and, to a lesser extent, BALB/c genetic background), and spontaneous development of chronic enterocolitis/inflammatory bowel disease. As The Jackson Laboratory Repository maintains mice at high health status conditions (high SPF), the observed or experimentally-induced Il10-deficient phenotype may vary from that previously published using mice from conventional mouse rooms.
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.
Stock No. 021872: IL-10-deficient BXSB.Yaa mice (BXSB.IL10-/- or BXSB.Yaa Il10-/-) are a BXSB-congenic strain carrying the interleukin 10 null mutation. Homozygous (IL10-/-) mice are viable and fertile.
Compared to BXSB/MpJ, deficiency of this anti-inflammatory cytokine in BXSB.IL10-/- mice leads to an accelerated and more severe spontaneous autoimmune phenotype. Specifically, mortality in BXSB.IL10-/- males starts at ~10 weeks of age with 50% lethality by ~22 weeks of age. Compared to males, the BXSB.IL10-/- females develop a greatly attenuated form of autoimmune disease. The donating investigator reports that BXSB.IL10-/- mice exhibit no signs of inflammatory bowel disease.
Heterozygous males (BXSB.IL10+/-) 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-10 null allele are described and available from The Jackson Laboratory Repository as Stock No. 002251.
The IL-10 null allele (Il10tm1Cgn) was designed by Dr. Werner Muller (University of Cologne) to replace codons 5-55 of exon 1 with a 24 bp linker (providing a termination codon) and neomycin resistance cassette, as well as introduce a termination codon into exon 3 of the interleukin 10 gene on chromosome 1. C57BL/6J-congenic mice harboring this IL-10 null allele are described and available from The Jackson Laboratory Repository as Stock No. 002251.
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.IL10-/- mice at generation N11F12 to The Jackson Laboratory Repository (Autoimmune Resource) to establish Stock No. 021872. Male mice have the BXSB/MpJ-derived Y chromosome that contains the Y-linked autoimmune accelerator locus (Yaa).
|Allele Name||targeted mutation 1, University of Cologne|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||IL-10-; Il10-; IL-10 KO; IL-10KO; Il10tmCgn; IL-10KO|
|Gene Symbol and Name||Il10, interleukin 10|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A 500 bp genomic fragment containing codons 5-55 was replaced with a linker containing a termination codon followed by a neomycin cassette. A termination codon was also introduced into exon 3. No IL10 activity was detectable by ELISA assays in supernatants of in vitro cultures of Con A-stimulated splenic T cells derived from homozygous mice following infection with the nematode N. brasiliensis.|
|Mutations Made By|| |
Dr. Ralf Kuhn, Max-Delbrück Center for Molecular Medicine
To maintain the live colony, homozygous mice may be bred together. Homozygous mice are viable and fertile, but exhibit a similar but accelerated autoimmune disease compared to BXSB/MpJ inbred mice (Stock No. 000740). Specifically, mortality in BXSB.IL10-/- males starts at ~10 weeks of age with 50% lethality by ~22 weeks of age. Compared to males, the BXSB.IL10-/- females develop a greatly attenuated form of autoimmune disease. Heterozygotes will develop the sex-specific autoimmune phenotype of BXSB/MpJ. The expected coat color is white-bellied agouti.
As homozygous mice are more susceptible to pathogenic bacteria, high specific pathogen-free (SPF) conditions are recommended for optimal breeding. However, the onset and severity of any spontaneous or experimentally-induced inflammatory phenotype of Il10-deficient mice is strongly influenced by the genetic background and the husbandry conditions (specific health status/commensal flora) of the vivaria in which mice are maintained and such high SPF conditions may attenuate the desired Il10-deficient phenotype.
When using the BXSB.129P2(B6)-Il10tm1Cgn/DcrJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #021872 in your Materials and Methods section.