B6.129P2-Il10^tm1Cgn/J

Stock number: 002251
Product name: Il-10 KO
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research

Description

B6.129P2-Il10^tm1Cgn/J mutant mice spontaneously develop a chronic inflammatory bowel disease (IBD). Il10-deficiency is associated with altered lymphocyte and myeloid profiles, elevated serum amyloid A levels, altered responses to inflammatory or autoimmune stimuli, increased prevalence of colorectal adenocarcinoma, and spontaneous development of chronic enterocolitis. Il10-deficient mice exhibit a significant increase in peripheral blood granulocyte populations upon lesion development.

Detailed description

Mice homozygous for the Il10^tm1Cgn targeted mutation are viable and fertile when housed under specific pathogen free (SPF) conditions. 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 (see below). As The Jackson Laboratory Repository maintains these 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. These IL-10 mutant mice may be useful studying inflammatory bowel disease (IBD) (Crohn's disease (CD) and/or colitis), cancer, innate and adaptive immunity, and many other areas of inflammatory or autoimmunity research.

The onset and severity of both spontaneous and 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.
For example, inflammatory bowel disease (IBD; colitis and Crohn's disease) severity in mouse models is dependent upon interactions between specific genetic background and environmental factors (an as yet undefined component of the enteric flora of which Helicobacter spp. appear to be associated, but not specifically the environmental trigger). Both spontaneous and induced models of IBD demonstrate that susceptibility to intestinal inflammation varies markedly among inbred strains of mice. Generally, for Il10-deficient models on defined genetic backgrounds, the severity of colitis-related characteristics is most severe on C3H/HeJBir (Stock No. 004326 and Stock No. 003968) or 129/Sv (Stock No. 004368), intermediate on BALB/cJ (Stock No. 004333) or NOD/Lt (Stock No. 004266), and least severe on C57BL/10 (Stock No. 002250) or C57BL/6J (Stock No. 002251). Furthermore, the husbandry conditions (specific health status/commensal flora) of the vivaria in which mice are maintained significantly alter the onset and severity of spontaneous IBD; higher SPF conditions are associated with attenuated colitis. Il10-deficient mice on both the C3H/HeJBir and C57BL/6J genetic backgrounds exhibit a significant increase in peripheral blood granulocyte populations upon lesion development and this metric may be used as a robust non-lethal assessment of Il10-deficiency induced colitis onset and severity. Other indications of Il10-deficiency induced colitic lesion onset may include perianal ulceration (C3H/HeJBir background) or rectal prolapse (C57BL/6J background).

Under the conditions described in Maite et al., 2023 Int. J. Mol. Sci. 24:10364, C57BL/6-congenic IL-10-deficient females were more prone than knock-out males to develop spontaneous intestinal inflammation, with an increase in fecal miR-21, and dysbiosis with more detrimental characteristics.

Development

The Il10^tm1Cgn mutation was created by in the Laboratory of Dr. Werner Muller at the University of Cologne. Briefly, a targeting vector was designed to replace codons 5-55 of exon 1 of the targeted gene with a 24 bp linker (providing a termination codon) and a neo expression cassette, as well as introduce a termination codon into exon 3. The construct was electroporated into 129P2/OlaHsd-derived E14-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6 blastocysts and chimeric males were bred with C57BL/6 females to establish the mutant colony on a mixed B6;129P2 genetic background. Subsequently, mutant mice were backcrossed to the C57BL/6J genetic background for several generations to generate this strain.

Allele

Symbol: Il10^tm1Cgn
Name: targeted mutation 1, University of Cologne
MGI accession ID: MGI:1857199
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: IL-10-; Il10-; IL-10 KO; IL-10^KO; Il10^tmCgn; IL-10KO
Marker symbol: Il10
Marker name: interleukin 10
Marker synonyms: CSIF; cytokine synthesis inhibitory factor; GVHDS; If2a; IL-10; IL10A; IL10X; TGIF
Chromosome: 1
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.