Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.CBA-Tg(Il1rn)1Dih/J    (Changed: 16-SEP-05 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System +/+ sibling x Hemizygote         (Female x Male)   11-SEP-08 Species laboratory mouse Generation N20p (12-FEB-06) Generation Definitions   Donating Investigator Emmet Hirsch,   Northwestern University

Description
These transgenic mice overexpress the secreted mouse Il1rn under the control of endogenous regulatory elements. The transgene contains the sequence encoding the secreted protein with a point mutation (G to A) in exon 3. These mice have an estimated 8 copies of the transgene in tandem array. Northern blot analysis of liver tissue following lipopolysaccharide (LPS) endotoxin challenge detects overexpression. RT-PCR analysis of corneal tissue detects higher levels of gene product (mRNA) than wildtype controls. The Donating Investigator reports that hemizygous mice are viable and fertile, whereas homozygous mice are sickly and die prematurely. Transgenic mice are less susceptible to LPS challenge than wildtype controls, but are more susceptible to experimental Listeria monocytogenes infection. Following endotoxin (LPS) challenge serum IL-1 levels are higher. Mice hemizygous for the transgene exhibit an intermediate susceptibility. Severity of stromal keratitis caused by herpes simplex virus (HSV) ocular infection is diminished. Mice with HSV ocular infection display reduced angiogenesis in the cornea, reduced polymorphonuclear leukocyte infiltration, decreased levels of macrophage-inflammatory protein 2 (MIP-2), IL-6, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2)levels, and delayed viral clearance. This mutant mouse strain may be useful in studies of inflammation and cytokine regulation.

Development
A transgenic construct containing the sequence encoding the mouse Il1rn gene (secreted protein) with a site directed mutation (G to A) in exon 3 was injected into fertilized B6CBAF2 eggs. The resulting transgenic mice, founder line 14, were backcrossed to the B6CBAF1/J background for an unspecified number of generations before being backcrossed for more than 20 generations onto the C57BL/6J background.

Control Information

	Control
	Noncarrier
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Il1rn

004754

B6.129S-Il1rntm1Dih/J

View Strains carrying other alleles of Il1rn     (1 strain)

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Tg(Il1rn)1Dih/0

        involves: C57BL/6 * CBA

• cardiovascular system phenotype
• abnormal angiogenesis
  • reduced angiogenesis observed in stromal keratitis caused by herpes simplex virus (HSV) ocular infection, reduced vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) levels   (MGI Ref ID J:88605)
• immune system phenotype
• abnormal circulating serum amyloid protein level
  • 30% decrease in serum amyloid P levels after subcutaneous turpentine administration   (MGI Ref ID J:61600)
• decreased circulating interleukin-6 level
  • reduced IL-6 levels in response to stromal keratitis caused by herpes simplex virus (HSV) ocular infection   (MGI Ref ID J:88605)
• decreased inflammatory response
  • reduced polymorphonuclear leukocyte infiltration in response to stromal keratitis caused by herpes simplex virus (HSV) ocular infection   (MGI Ref ID J:88605)
• • decreased susceptibility to endotoxin shock
    • less susceptible to lipopolysaccharide (LPS) endotoxin challenge, hemizygotes exhibit an intermediate phenotype when compared to wild-type and homozygous   (MGI Ref ID J:36387)
• decreased susceptibility to viral infection
  • severity of stromal keratitis caused by herpes simplex virus (HSV) ocular infection is diminished   (MGI Ref ID J:88605)
• increased susceptibility to bacterial infection
  • more susceptible to experimental Listeria monocytogenes infection, hemizygotes exhibit an intermediate phenotype when compared to wild-type and homozygous   (MGI Ref ID J:36387)
• homeostasis/metabolism phenotype
• abnormal circulating serum amyloid protein level
  • 30% decrease in serum amyloid P levels after subcutaneous turpentine administration   (MGI Ref ID J:61600)
• decreased circulating interleukin-6 level
  • reduced IL-6 levels in response to stromal keratitis caused by herpes simplex virus (HSV) ocular infection   (MGI Ref ID J:88605)

Tg(Il1rn)1Dih/Tg(Il1rn)1Dih

        involves: C57BL/6 * CBA

• immune system phenotype
• decreased susceptibility to endotoxin shock
  • less susceptible to lipopolysaccharide (LPS) endotoxin challenge   (MGI Ref ID J:36387)
• increased circulating interleukin-1 level
  • serum IL-1 levels are higher following lipopolysaccharide (LPS) endotoxin challenge   (MGI Ref ID J:36387)
• increased susceptibility to bacterial infection
  • more susceptible to experimental Listeria monocytogenes infection   (MGI Ref ID J:36387)
• homeostasis/metabolism phenotype
• increased circulating interleukin-1 level
  • serum IL-1 levels are higher following lipopolysaccharide (LPS) endotoxin challenge   (MGI Ref ID J:36387)

View Research Applications

Research Applications

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

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      genes regulating susceptibility to infectious disease and endotoxin
Growth Factors/Receptors/Cytokines

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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(Il1rn)1Dih
Allele Name		transgene insertion 1, David Hirsh
Allele Type		Transgenic (random, expressed)
Common Name(s)		IL-1ratg; IL1ra Tg;
Mutation Made By		Emmet Hirsch,   Northwestern University
Strain of Origin		(C57BL/6J x CBA)F2
Expressed Gene		Il1rn, interleukin 1 receptor antagonist, mouse, laboratory
Promoter		Il1rn, interleukin 1 receptor antagonist, mouse, laboratory
Molecular Note		This transgene contains the sequence encoding the secreted gene protein and approximately 2.0kb of upstream and 2.5kb of downstream untranslated flanking regions, and a site directed mutation (G to A) in exon 3. Northern blot analysis of liver tissue following LPS challenge detects overexpression. Two lines were created and called T14 and T16. [MGI Ref ID J:36387]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Il1rn)1Dih, Pyrosequencing
Tg(Il1rn)1Dih, Restriction Enzyme Digest

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

Tg(Il1rn)1Dih 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]

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]

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]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, hemizygous mice are bred to wildtype siblings.
Mating System	+/+ sibling x Hemizygote         (Female x Male)   11-SEP-08

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Noncarrier
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

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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