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Strain Name:

C.129P2(B6)-Il10tm1Cgn/J

Stock Number:

004333

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Former Name      C.129-Il10tm1Cgn    (Changed: 15-DEC-04 )
Genes & Alleles   Il10;   Il10tm1Cgn;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Targeted Mutation
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Background Strain BALB/cJ
Donating Investigator Donna Rennick,   DNAX Research Institute
GenerationN18+F14 (04-DEC-07)

Strain Description
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 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).

For a more detailed description please refer to the JAX Notes Fall 1997 article.

Strain Development
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 BALB/c genetic background for several generations to generate this strain. Simple sequence length polymorphism (SSLP) analysis confirmed that there are no chromosomal segments derived from 129 or C57BL/6, except for regions immediately flanking the disrupted locus.

Related Disease (OMIM) Terms

Inflammatory Bowel Disease 1; IBD1
Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Il10tm1Cgn/Il10tm1Cgn

        involves: 129P2/OlaHsd * C57BL/6
  • digestive/alimentary phenotype
  • abnormal colon morphology (MGI Ref ID J:107077)
    • colonic prolapse is observed in some older mutants
  • abnormal intestinal mucosa morphology (MGI Ref ID J:68476)
    • at 9 weeks, 59% of mice displaying colitis develop a high grade dysplasia of the colonic mucosa
  • intestinal inflammation (MGI Ref ID J:15222)
    • enterocolitis involving the entire intestinal tract, duodenum, proximal jejunum, and proximal colon
    • inflammation was limited to the proximal colon under specific pathogen free conditions
    • spontaneous inflammatory bowel disease (IBD) develops by 5 weeks in some animals
    • colitis (MGI Ref ID J:68476)
      • all Il10-null mice develop colitis by the age of 9 weeks in contrast to wild type littermates
  • growth/size phenotype
  • postnatal growth retardation (MGI Ref ID J:15222)
  • hematopoietic system phenotype
  • anemia (MGI Ref ID J:15222)
  • increased thymus weight (MGI Ref ID J:107077)
    • increases with time and IBD
  • thymus hyperplasia (MGI Ref ID J:107077)
    • increases with time and IBD
  • immune system phenotype
  • *normal* immune system phenotype (MGI Ref ID J:107077)
    • B and T lymphocytes develop normally
    • normal immune response to T cell-dependent immunization
    • abnormal interferon level (MGI Ref ID J:107077)
      • IFNgamma is expressed in colon in mice with minor IBD symptoms
    • abnormal interleukin level (MGI Ref ID J:107077)
      • Il-2, but not Il-1beta is expressed in colon in mice with minor IBD symptoms
    • abnormal tumor necrosis factor level (MGI Ref ID J:107077)
      • TNFalpha is expressed in colon in mice with minor IBD symptoms
    • chronic inflammation (MGI Ref ID J:15222)
      • enterocolitis involving the entire intestinal tract, duodenum, proximal jejunum, and proximal colon
      • inflammation was limited to the proximal colon under specific pathogen free conditions
    • increased IgE level (MGI Ref ID J:62283)
      • total IgE levels are more than 7-fold higher and serum levels of OVA-specific IgE more than 2-fold higher than in wild type mice after ovalbumin challenge
    • increased IgG1 level (MGI Ref ID J:62283)
      • OVA-specific IgG1 levels are higher in ovalbumin-sensitized mutants
    • increased IgG2a level (MGI Ref ID J:62283)
      • OVA-specific IgG2a levels are higher in ovalbumin-sensitized mutants
    • increased susceptibility to parasitic infection (MGI Ref ID J:123927)
      • time to death induced by exposure to Plasmodium falciparum is decreased compared to in wild type mice (7+/-0 days compared to 7.8+/-0.2 days, respectively)
      • in mice depleted of regulatory T cells, experimental cerebral malaria is delayed following exposure to Plasmodium falciparum but disease progression occurs unlike in wild type mice similarly treated
    • increased thymus weight (MGI Ref ID J:107077)
      • increases with time and IBD
    • intestinal inflammation (MGI Ref ID J:15222)
      • enterocolitis involving the entire intestinal tract, duodenum, proximal jejunum, and proximal colon
      • inflammation was limited to the proximal colon under specific pathogen free conditions
      • spontaneous inflammatory bowel disease (IBD) develops by 5 weeks in some animals
      • colitis (MGI Ref ID J:68476)
        • all Il10-null mice develop colitis by the age of 9 weeks in contrast to wild type littermates
    • thymus hyperplasia (MGI Ref ID J:107077)
      • increases with time and IBD
  • tumorigenesis
  • intestinal adenocarcinoma (MGI Ref ID J:68476)
    • at 9 weeks, 13% of homozygotes have adenocarcinomas
    • in 10-31 week old animals, there is a 65% incidence of colorectal carcinomas
  • respiratory system phenotype
  • decreased airway responsiveness (MGI Ref ID J:62283)
    • mutants sensitized and challenged to ovalbumin (OVA) fail to develop airway hyper-responsiveness despite a significant eosinophilic airway inflammatory response
    • mutants are hyporesponsive to electrical field stimulation of trachea smooth muscle after OVA aerosol challenge
  • cardiovascular system phenotype
  • abnormal leukotriene physiology (MGI Ref ID J:62283)
    • OVA-sensitized mutants exhibit higher eosinophil peroxidase and leukotriene levels in bronchoalveolar lavage fluid than wild type mice
  • homeostasis/metabolism phenotype
  • abnormal interferon level (MGI Ref ID J:107077)
    • IFNgamma is expressed in colon in mice with minor IBD symptoms
  • abnormal interleukin level (MGI Ref ID J:107077)
    • Il-2, but not Il-1beta is expressed in colon in mice with minor IBD symptoms
  • abnormal tumor necrosis factor level (MGI Ref ID J:107077)
    • TNFalpha is expressed in colon in mice with minor IBD symptoms

Il10tm1Cgn/Il10tm1Cgn

        involves: 129P2/OlaHsd
  • immune system phenotype
  • abnormal inflammatory response (MGI Ref ID J:117122)
    • after three subcutaneous injections of LPS into the flank, mice develop solid subcutaneous swellings whereas wild type do not
    • lesion is associated with infiltration of macrophages and neutrophils, edema, and extensive necrosis of dermal, epidermal, and muscle layers of skin
    • 5 days after flank injection of CpG, mice develop solid subcutaneous swellings at the injection site; lesions show conspicuous edema, massive infiltration by macrophages and neutrophilic granulocytes, and extensive necrosis of the dermis, epidermis and muscle layer of the skin while lesions in controls do not display edema or necrosis and show infiltration by macrophages primarily
    • abnormal cytokine secretion (MGI Ref ID J:117122)
      • 6 hours after LPS injection, TNF, Il12 and Ifng levels are substantially higher than in controls
    • increased susceptibility to endotoxin shock (MGI Ref ID J:117122)
      • i.p. injection of LPS results in death in all animal by 48 hours, compared to survival of 23/25 controls
    • intestinal inflammation (MGI Ref ID J:113376)
      • mice show exaggerated inflammatory response upon exposure to CML-mps-containing eluate compared to control
  • digestive/alimentary phenotype
  • intestinal inflammation (MGI Ref ID J:113376)
    • mice show exaggerated inflammatory response upon exposure to CML-mps-containing eluate compared to control
  • reproductive system phenotype
  • abnormal reproductive system physiology (MGI Ref ID J:130208)
    • mice treated with Gal1 exhibit less protection from stress-induced fetal loss compared to similarly treated wild type mice

Il10tm1Cgn/Il10tm1Cgn

        B6.129P2-Il10tm1Cgn/J
  • immune system phenotype
  • abnormal regulatory T cell physiology (MGI Ref ID J:125748)
    • CD25-positive CD4 T cells from these mice fail to protect against the wasting disease induced by transferring naïve CD4 T cells into immunodeficient hosts
    • however, CD25-postive CD4 T cells inhibit the expansion of naive T cells in Rag2 deficient hosts as effectively as wild type CD25-positive CD4 T cells

Gene & Allele Details

Allele Symbol Il10tm1Cgn
Allele Name targeted mutation 1, University of Cologne
Common Name(s) IL-10 KO; IL-10-; IL-10KO; IL-10KO; Il10-;
Mutation Made By Ralf Kuhn,   University of Cologne
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14.1
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Il10, interleukin 10
Chromosome 1
Gene Common Name(s) CSIF; IL-10; IL10A; Il-10; MGC126450; MGC126451; TGIF; cytokine synthesis inhibitory factor;
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 in ELISA assays in supernatants of in vitro splenic T cells derived from homozygous mice.

Control Information

  Allele   Control
 Il10tm1Cgn  000651 BALB/cJ
 
  Considerations for Choosing Controls

Genotyping Protocols

Il10tm1Cgn

Colony Maintenance

Breeding & HusbandryThis strain originated on a B6;129P2 background and has been backcrossed for 18 generations on the BALB/cJ (Stock No. 000651) background. 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.
Diet Information LabDiet® 5K52/5K67

Related Strains

View Strains carrying   Il10tm1Cgn     (10 strains)

Additional Web Information

Congenic Nomenclature

Animal Health Reports

Room Number           AX12

Research Applications

This mouse can be used to support research in many areas including:

Cancer Research
Increased Tumor Incidence (Adenomas: intestinal adenomas)

Cell Biology Research
Genes Regulating Growth and Proliferation

Immunology and Inflammation Research
Lymphoid Tissue Defects (myeloid hyperplasia)

Internal/Organ Research
Gastrointestinal Defects (colitis)

Il10tm1Cgn related

Cancer Research
Growth Factors/Receptors/Cytokines

Hematological Research
Anemia, Iron Deficiency and Transport Defects (hemolytic)
Immunological Defects

Immunology and Inflammation Research
Autoimmunity
Growth Factors/Receptors/Cytokines
Immunodeficiency
Inflammation (Inflammatory bowel disease)

References

Selected Reference(s)

Berg DJ; Davidson N; Kuhn R; Muller W; Menon S; Holland G; Thompson-Snipes L; Leach MW; Rennick D. 1996. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest 98(4):1010-20. [PubMed: 8770874]  [MGI Ref ID J:35020]

Additional References

Price and Supply Information

Strain Name: C.129P2(B6)-Il10tm1Cgn/J
Stock Number: 004333

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
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Control InformationView Control Information in Strain Details.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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