Strain Name:

B6.129S-Il1rntm1Dih/J

Stock Number:

004754

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
These Il1rn knock-out mice have decreased body mass compared with wild-type controls, and are more susceptible than controls to lethal endotoxemia. They are suitable for use in applications related to the study of inflammation and cytokine regulation.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   24-AUG-06
Specieslaboratory mouse
GenerationN25+N2F15 (13-DEC-13)
Generation Definitions
 
Donating InvestigatorDr. Emmet Hirsch,   Northwestern University

Description
Mice that are homozygous for the targeted mutation are viable and do not display any gross physical or behavioral abnormalities. By 6 weeks of age homozygous mice have lower body weight. Homozygous females may have reduced litter sizes. No gene product (mRNA) is detected by Northern blot analysis of lung tissue after lipopolysaccharide (LPS) challenge. Mice homozygous for the mutation are less susceptible to experimental Listeria monocytogenes infection, but are more susceptible to LPS endotoxin challenge. After LPS challenge IL-1 levels are decreased. Basal serum amyloid protein and serum IL-6 levels are higher. Hepatic acute phase protein inflammatory response and mortality to subcutaneous turpentine abscess induction are increased. When fed a high fat diet containing cholate for 12 weeks, homozygotes exhibit a 3-fold decrease in total cholesterol (non-HDL). Heterozygotes fed the same diet exhibit an intermediate decrease in total cholesterol. Immunohistochemical analysis of homozygotes fed the high fat diet did not detect any gene product in the proximal aorta. This mutant mouse strain may be useful in studies of inflammation and cytokine regulation.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes and a site directed mutation (G to A) in exon 3 was used to disrupt exon 3, which encodes the secreted gene product (protein). The construct was electroporated into derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to the same for more than 25 generations.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Il1rn
004753   B6.Cg-Tg(Il1rn)1Dih/J
View Strains carrying other alleles of Il1rn     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Gastric Cancer, Hereditary Diffuse; HDGC   (IL1RN)
Microvascular Complications of Diabetes, Susceptibility to, 4; MVCD4   (IL1RN)
Osteomyelitis, Sterile Multifocal, with Periostitis and Pustulosis;   (IL1RN)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Il1rntm1Dih/Il1rntm1Dih

        B6.129S-Il1rntm1Dih
  • homeostasis/metabolism phenotype
  • decreased circulating cholesterol level
    • 3-fold decrease in non-HDL cholesterol when fed high fat diet containing cholate for 12 weeks   (MGI Ref ID J:76336)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Il1rntm1Dih/Il1rn+

        involves: 129S/SvEv * C57BL/6J
  • growth/size/body phenotype
  • decreased body weight
    • heterozygotes exhibit an intermediate phenotype when compared to wild-type and homozygous mice   (MGI Ref ID J:36387)
  • immune system phenotype
  • decreased susceptibility to bacterial infection
    • less susceptible to experimental Listeria monocytogenes infection, heterozygotes display an intermediate phenotype   (MGI Ref ID J:36387)
  • increased susceptibility to endotoxin shock
    • more susceptible to lipopolysaccharide (LPS) endotoxin challenge   (MGI Ref ID J:36387)

Il1rntm1Dih/Il1rntm1Dih

        involves: 129S/SvEv * C57BL/6J
  • growth/size/body phenotype
  • decreased body weight
    • lower body weight apparent by 6 weeks of age   (MGI Ref ID J:36387)
  • immune system phenotype
  • abnormal circulating serum amyloid protein level
    • increased basal serum amyloid P levels   (MGI Ref ID J:61600)
  • decreased circulating interleukin-1 level
    • decreased serum levels of IL1 after endotoxin exposure   (MGI Ref ID J:36387)
  • decreased susceptibility to bacterial infection
    • less susceptible to experimental Listeria monocytogenes infection   (MGI Ref ID J:36387)
  • increased acute inflammation   (MGI Ref ID J:88605)
    • increased hepatic acute phase protein response to subcutaneous turpentine administration, increased mortality to turpentine abscess induction: 50% of mice died by day 5   (MGI Ref ID J:61600)
    • increased susceptibility to endotoxin shock
      • more susceptible to lipopolysaccharide (LPS) endotoxin challenge   (MGI Ref ID J:36387)
  • increased circulating interleukin-6 level
    • increased basal serum IL6 levels   (MGI Ref ID J:61600)
  • reproductive system phenotype
  • reduced fertility
    • decreased number of offspring   (MGI Ref ID J:61600)
  • homeostasis/metabolism phenotype
  • abnormal circulating serum amyloid protein level
    • increased basal serum amyloid P levels   (MGI Ref ID J:61600)
  • decreased circulating cholesterol level
    • 3-fold decrease in non-HDL cholesterol when fed high fat diet containing cholate for 12 weeks   (MGI Ref ID J:76336)
  • decreased circulating interleukin-1 level
    • decreased serum levels of IL1 after endotoxin exposure   (MGI Ref ID J:36387)
  • increased circulating interleukin-6 level
    • increased basal serum IL6 levels   (MGI Ref ID J:61600)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Inflammation

Research Tools
Immunology, Inflammation and Autoimmunity Research
      genes regulating susceptibility to infectious disease and endotoxin

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Il1rntm1Dih
Allele Name targeted mutation 1, David Hirsh
Allele Type Targeted (Null/Knockout)
Common Name(s) IL-1ra-; rako;
Strain of Origin129S/SvEv-Gpi1
ES Cell Line NameCCE/EK.CCE
ES Cell Line Strain129S/SvEv-Gpi1
Gene Symbol and Name Il1rn, interleukin 1 receptor antagonist
Chromosome 2
Gene Common Name(s) DIRA; F630041P17Rik; ICIL-1RA; IL-1RN; IL-1ra; IL-1ra3; IL1F3; IL1RA; IRAP; MVCD4; RIKEN cDNA F630041P17 gene;
Molecular Note Insertion of a neomycin resistance cassette into exon III disrupted the sequence encoding the secreted protein. Northern blot analysis of lung tissue collected after LPS injection did not detect transcript in homozygous mutant mice. [MGI Ref ID J:36387]

Genotyping

Genotyping Information

Genotyping Protocols

Il1rntm1Dih, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Hirsch E; Irikura VM; Paul SM; Hirsh D. 1996. Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. Proc Natl Acad Sci U S A 93(20):11008-13. [PubMed: 8855299]  [MGI Ref ID J:36387]

Additional References

Il1rntm1Dih related

Biswas PS; Banerjee K; Kim B; Rouse BT. 2004. Mice transgenic for IL-1 receptor antagonist protein are resistant to herpetic stromal keratitis: possible role for IL-1 in herpetic stromal keratitis pathogenesis. J Immunol 172(6):3736-44. [PubMed: 15004178]  [MGI Ref ID J:88605]

Bunt SK; Clements VK; Hanson EM; Sinha P; Ostrand-Rosenberg S. 2009. Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4. J Leukoc Biol 85(6):996-1004. [PubMed: 19261929]  [MGI Ref ID J:149766]

Bunt SK; Yang L; Sinha P; Clements VK; Leips J; Ostrand-Rosenberg S. 2007. Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res 67(20):10019-26. [PubMed: 17942936]  [MGI Ref ID J:126013]

Devlin CM; Kuriakose G; Hirsch E; Tabas I. 2002. Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size. Proc Natl Acad Sci U S A 99(9):6280-5. [PubMed: 11983917]  [MGI Ref ID J:76336]

Hudock KM; Liu Y; Mei J; Marino RC; Hale JE; Dai N; Worthen GS. 2012. Delayed resolution of lung inflammation in Il-1rn-/- mice reflects elevated IL-17A/granulocyte colony-stimulating factor expression. Am J Respir Cell Mol Biol 47(4):436-44. [PubMed: 22592923]  [MGI Ref ID J:201242]

Irikura VM; Lagraoui M; Hirsh D. 2002. The epistatic interrelationships of IL-1, IL-1 receptor antagonist, and the type I IL-1 receptor. J Immunol 169(1):393-8. [PubMed: 12077269]  [MGI Ref ID J:123841]

Josephs MD; Solorzano CC; Taylor M; Rosenberg JJ; Topping D; Abouhamze A; Mackay SL; Hirsch E; Hirsh D; Labow M; Moldawer LL. 2000. Modulation of the acute phase response by altered expression of the IL-1 type 1 receptor or IL-1ra. Am J Physiol Regul Integr Comp Physiol 278(4):R824-30. [PubMed: 10749768]  [MGI Ref ID J:61600]

Ma Y; Thornton S; Boivin GP; Hirsh D; Hirsch R; Hirsch E. 1998. Altered susceptibility to collagen-induced arthritis in transgenic mice with aberrant expression of interleukin-1 receptor antagonist. Arthritis Rheum 41(10):1798-805. [PubMed: 9778220]  [MGI Ref ID J:134110]

Merhi-Soussi F; Kwak BR; Magne D; Chadjichristos C; Berti M; Pelli G; James RW; Mach F; Gabay C. 2005. Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice. Cardiovasc Res 66(3):583-93. [PubMed: 15914123]  [MGI Ref ID J:132570]

Nagarajan UM; Sikes JD; Yeruva L; Prantner D. 2012. Significant Role of IL-1 Signaling, but Limited Role of Inflammasome Activation, in Oviduct Pathology during Chlamydia muridarum Genital Infection. J Immunol 188(6):2866-75. [PubMed: 22331066]  [MGI Ref ID J:181842]

Ramos HJ; Lanteri MC; Blahnik G; Negash A; Suthar MS; Brassil MM; Sodhi K; Treuting PM; Busch MP; Norris PJ; Gale M Jr. 2012. IL-1beta signaling promotes CNS-intrinsic immune control of West Nile virus infection. PLoS Pathog 8(11):e1003039. [PubMed: 23209411]  [MGI Ref ID J:195453]

Wong ML; Xie B; Beatini N; Phu P; Marathe S; Johns A; Gold PW; Hirsch E; Williams KJ; Licinio J; Tabas I. 2000. Acute systemic inflammation up-regulates secretory sphingomyelinase in vivo: A possible link between inflammatory cytokines and atherogenesis Proc Natl Acad Sci U S A 97(15):8681-6. [PubMed: 10890909]  [MGI Ref ID J:63405]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as heterozygotes, due to the reduced fertility of homozygous females.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   24-AUG-06
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00Female or MaleHeterozygous for Il1rntm1Dih  
$239.00Female or MaleHomozygous for Il1rntm1Dih  
Price per Pair (US dollars $)Pair Genotype
$478.00Heterozygous for Il1rntm1Dih x Heterozygous for Il1rntm1Dih  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70Female or MaleHeterozygous for Il1rntm1Dih  
$310.70Female or MaleHomozygous for Il1rntm1Dih  
Price per Pair (US dollars $)Pair Genotype
$621.40Heterozygous for Il1rntm1Dih x Heterozygous for Il1rntm1Dih  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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