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Strain Name:

C3Bir.129P2(B6)-Il10tm1Cgn/LtJ

Stock Number:

003968

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Former Name      C3Bir.129P2(B6)-Il10tm1Cgn/J    (Changed: 14-DEC-05 )
Genes & Alleles   Il10;   Il10tm1Cgn;   Pde6b;   Pde6brd1;   Tlr4;   Tlr4Lps-d;

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
Specieslaboratory mouse
Donating Investigator Edward Leiter,   The Jackson Laboratory
GenerationN16p (30-MAY-04)

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 C3H/HeJBir genetic background for at least 12 generations to generate this strain.

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.
 
Allele Symbol Pde6brd1
Allele Name retinal degeneration 1
Common Name(s) rd; rd-1; rd1; rodless retina;
 
Allele Symbol Tlr4Lps-d
Allele Name defective lipopolysaccharide response
Common Name(s) TLR4-Mu; Tlr4-; Tlr4d; TlrLps-d; lpsd;
Strain of OriginC3H/HeJ
Gene Symbol and Name Tlr4, toll-like receptor 4
Chromosome 4
Gene Common Name(s) ARMD10; CD284; Lps; RAS-like, family 2, locus 8; Rasl2-8; TOLL; hToll; lipopolysaccharide response;
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. [MGI Ref ID J:51522] [MGI Ref ID J:53519] [MGI Ref ID J:57938]

Control Information

  Allele   Control
 Il10tm1Cgn  None Available
 
  Considerations for Choosing Controls

Genotyping Protocols

Il10tm1Cgn

Colony Maintenance

Breeding & HusbandryWhen 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)

Strains carrying   Pde6brd1 allele
004202   B6.C3 Pde6brd1 Hps4le/+ +-Lmx1adr-8J/J
000002   B6.C3-Pde6brd1 Hps4le/J
001022   B6C3FeF1/J a/a
000652   BDP/J
000653   BUB/BnJ
002439   C3.129P2(B6)-B2mtm1Unc/J
005494   C3.129S1(B6)-Grm1rcw/J
000480   C3.MRL-Faslpr/J
001957   C3A Pde6brd1.O20/A-Prph2Rd2/J
005973   C3Bir.129P2(B6)-Il10C3Bir/LtJ
004326   C3Bir.129P2(B6)-Il10tm1Cgn/Lt
001906   C3Ga.Cg-Catb/J
001904   C3H-Atcayji-hes/J
000659   C3H/HeJ
000784   C3H/HeJ-Faslgld/J
000509   C3H/HeJ-Lystbg-2J/J
002433   C3H/HeJ-Spnb4qv-lnd2J/J
005972   C3H/HeJBirLtJ
001824   C3H/HeJSxJ
000635   C3H/HeOuJ
000474   C3H/HeSn
001431   C3H/HeSn-ocd/J
000661   C3H/HeSnJ
002235   C3H/HeSnJ-Ctnna2cdf/J
002333   C3H/HeSnJ-gri/J
006435   C3HeB.SW-Soaa/MonJ
000658   C3HeB/FeJ
001576   C3HeB/FeJ-Atp7btx-J/J
002588   C3HeB/FeJ-Eya1bor/J
001533   C3HeB/FeJ-Mc1rE-so Gli3Xt-J/J
001886   C3HeB/FeJLe a/a-gnd/J
001908   C3HfB/BiJ
001502   C3Sn.B6-Epha4rb/J
001547   C3Sn.Cg-Cm/J
000656   CBA/J
000813   CBA/J-Atp7aMo-pew/J
000660   DA/HuSnJ
000023   FL/1ReJ
000025   FL/4ReJ
003024   FVB.129P2(B6)-Fmr1tm1Cgr/J
002539   FVB.129P2-Abcb4tm1Bor/J
002935   FVB.129S2(B6)-Ccnd1tm1Wbg/J
002953   FVB.Cg-Tg(MMTVTGFA)254Rjc/J
003170   FVB.Cg-Tg(Myh6-tTA)6Smbf/J
003078   FVB.Cg-Tg(WapIgf1)39Dlr/J
003257   FVB/N-Tg(GFAPGFP)14Mes/J
002374   FVB/N-Tg(MMTV-PyVT)634Mul/J
002856   FVB/N-Tg(TIE2-lacZ)182Sato/J
002384   FVB/N-Tg(UcpDta)1Kz/J
001800   FVB/NJ
003487   FVB/NJ-Tg(XGFAP-lacZ)3Mes/J
001491   FVB/NMob
000734   MOLD/RkJ
000550   MOLF/EiJ
002423   NON/ShiLtJ
000679   P/J
000680   PL/J
100299   PLSJLF1/J
000269   SB/LeJ
005651   SJL.AK-Thy1a/TseJ
000686   SJL/J
000688   ST/bJ
004808   STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
002648   STOCK a/a Cln6nclf/J
000279   STOCK gr +/+ Ap3d1mh/J
005965   STOCK Tg(Pomc1-cre)16Lowl/J
004770   SW.B6-Soab/J
002023   SWR.M-Emv21 Emv22/J
000689   SWR/J
000939   SWR/J-Clcn1adr-mto/J
000692   WB/ReJ KitW/J
100410   WBB6F1/J-KitW/KitW-v/J
000693   WC/ReJ KitlSl/J
100401   WCB6F1/J KitlSl KitlSl-d
View Strains carrying   Pde6brd1     (74 strains)

Strains carrying   Tlr4Lps-d allele
002930   C.C3-Tlr4Lps-d/J
005973   C3Bir.129P2(B6)-Il10C3Bir/LtJ
004326   C3Bir.129P2(B6)-Il10tm1Cgn/Lt
000659   C3H/HeJ
005972   C3H/HeJBirLtJ
View Strains carrying   Tlr4Lps-d     (5 strains)

View Strains carrying other alleles of Pde6b     (8 strains)

Strains carrying other alleles of Tlr4
007227   B6.B10ScN-Tlr4lps-del/JthJ
003752   C57BL/10ScNJ
View Strains carrying other alleles of Tlr4     (2 strains)

Additional Web Information

Congenic Nomenclature

Research Applications

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

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)

Pde6brd1 related

Mouse/Human Gene Homologs
retinitis pigmentosa, autosomal recessive

Sensorineural Research
Retinal Degeneration

Tlr4Lps-d related

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers (Tlr deficiency)
Immunodeficiency (Tlr deficiency)
Inflammation (Tlr deficiency)

References

Selected Reference(s)

Bristol IJ; Farmer MA; Cong Y; Zheng XX; Strom TB; Elson CO; Sundberg JP; Leiter EH. 2000. Heritable susceptibility for colitis in mice induced by IL-10 deficiency. Inflamm Bowel Dis 6(4):290-302. [PubMed: 11149562]  [MGI Ref ID J:109882]

Additional References

Price and Supply Information

Strain Name: C3Bir.129P2(B6)-Il10tm1Cgn/LtJ
Stock Number: 003968

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
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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