This strain represents a genetic mouse model of inflammatory bowel disease (IBD) where stable inflammatory lesions in the cecum and colon are present by six to seven weeks of ages. The mice carry a targeted mutation of the interleukin 10 gene, one of several genes whose disruption induces IBD.
Dr. Edward Leiter, The Jackson Laboratory
Mice homozygous for the Il10tm1Cgn 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 this C3H/HeJBir background (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).
The Il10tm1Cgn 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 C3H/HeJBir genetic background for at least 12 generations to generate this strain.
|Allele Name||targeted mutation 1, University of Cologne|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||IL-10 KO; IL-10-; IL-10KO; IL-10KO; Il10-; Il10tmCgn|
|Gene Symbol and Name||Il10, interleukin 10|
|Gene Synonym(s)||CSIF; GVHDS; IL-10; IL10A; IL10X; Il-10; TGIF; cytokine synthesis inhibitory factor|
|Strain of Origin||129P2/OlaHsd|
|General Note||Phenotypic Similarity to Human Syndrome: Idiopathic Inflammatory Bowel Disease (J:15222).|
|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, University of Cologne
|Allele Name||defective lipopolysaccharide response|
|Allele Synonym(s)||TLR4-M; TLR4-Mu; TLR4lps-def; TLR4d; Tlr4-; Tlr4d; TlrLps-d; lpsd; mutant TLR4|
|Gene Symbol and Name||Tlr4, toll-like receptor 4|
|Gene Synonym(s)||ARMD10; CD284; Lps; Lps; RAS-like, family 2, locus 8; Rasl2-8; Rasl2-8; TLR-4; TOLL; lipopolysaccharide response; lipopolysaccharide response|
|Strain of Origin||C3H/HeJ|
|General Note||C3H/HeJ mice carry this allele. Various combinations of Lps-associated traits have been followed in crosses between C3H/HeJ and other C3H substrains, and the traits have in all cases segregated together (J:30692, J:5557, J:5593, J:5938). Some of the traits show dominance of the Tlr4lps-n allele; others, including Tlr4Lps-d, show codominance. |
Genbank ID for this allele: AF095353
|Molecular Note||This allele corresponds to a mutation in the third exon of the gene. A C to A substitution at nucleotide position 2342 results in an amino acid substitution that replaces proline with histidine at position 712.|
When maintaining a live colony, homozygous mice may be bred together. 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 both the 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 and such high SPF conditions may attenuate the desired Il10-deficient phenotype.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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