Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   19-APR-08 Species laboratory mouse Generation F?N5+N2F4 (06-MAR-13) Generation Definitions   Donating Investigator Tom Maniatis,   Harvard University

Description
Homozygous IKKepsilon mutant mice are viable and fertile. Homozygous deletion results in a complete loss of the endogenous kinase function in lung, spleen, and embryonic fibroblasts. These mice have increased susceptibility to viral infection due to defective inteferon (IFN) signaling. These IKKepsilon mutant mice may be useful in immunological studies involving IFN signaling and host responses to infection.

Development
The donating investigator reports that a targeting vector was used to replace exons 4-6 of the targeted gene with a PGK-neo cassette. The construct was electroporated into "B6/S129"-hybrid derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and chimeric offspring were bred to C57BL/6J mice. Heterozygous mutants were bred to inbred C57BL/6J mice for at least 5 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Ikbke^tm1Tman/Ikbke^tm1Tman

        B6.Cg-Ikbke^tm1Tman

• immune system phenotype
• increased susceptibility to viral infection
  • while at inoculations of >7 x10³ pfu, mutant and control mice show 100% mortality, mutants show greater susceptibility to infection by influenza at lower titers than control mice   (MGI Ref ID J:119791)
  • in infected primary mouse embryonic fibroblasts, rates of virus replication are similar to wild-type, while the titer continues to increase   (MGI Ref ID J:119791)
  • 7 days post-infection, lungs of mutants show increased immunopathology compared to wild-type   (MGI Ref ID J:119791)
• lung inflammation
  • 7 days post infection, mutant lungs display inflammatory infiltrate consisting of lymphocytes, macrophages, and neutrophils   (MGI Ref ID J:119791)
• growth/size phenotype
• weight loss
  • after inoculation with 700 pfu, both mutants and controls show a drop of >10% body weight, but mutants continue to lose weight to below 80% of their original body mass before mortality, whereas control mice do not   (MGI Ref ID J:119791)
• respiratory system phenotype
• lung inflammation
  • 7 days post infection, mutant lungs display inflammatory infiltrate consisting of lymphocytes, macrophages, and neutrophils   (MGI Ref ID J:119791)
• cellular phenotype
• abnormal cell physiology
  • in mutant fibroblasts, about 30% of IFN-stimulated genes (ISGs) are poorly induced by IFNgamma compared to induction in wild-type fibroblasts   (MGI Ref ID J:119791)

View Research Applications

Research Applications

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

Cancer Research
Growth Factors/Receptors/Cytokines

Cell Biology Research
Signal Transduction

Hematological Research
Immunological Defects

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      genes regulating susceptibility to infectious disease and endotoxin
Growth Factors/Receptors/Cytokines
Immunodeficiency
      multiple immune defects
Intracellular Signaling Molecules
Lymphoid Tissue Defects

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

Virology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ikbketm1Tman
Allele Name		targeted mutation 1, Tom Maniatis
Allele Type		Targeted (knock-out)
Common Name(s)		Ikbke-;
Mutation Made By		Tom Maniatis,   Harvard University
Strain of Origin		129 and C57BL/6
ES Cell Line Strain		129
Gene Symbol and Name		Ikbke, inhibitor of kappaB kinase epsilon
Chromosome		1
Gene Common Name(s)		AW558201; IKK-E; IKK-i; IKKE; IKKI; IKKepsilon; expressed sequence AW558201;
Molecular Note		Exons 4-6 of the targeted gene were replaced with a PGK-neo cassette. Mice show a complete loss of the endogenous kinase function in lung, spleen, and embryonic fibroblasts. [MGI Ref ID J:119791]

Genotyping

Genotyping Information

Genotyping Protocols

Ikbke^tm1Tman, Separated PCR
NEOTD (Generic Neo), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Tenoever BR; Ng SL; Chua MA; McWhirter SM; Garcia-Sastre A; Maniatis T. 2007. Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity. Science 315(5816):1274-8. [PubMed: 17332413]  [MGI Ref ID J:119791]

Additional References

Ikbke^tm1Tman related

Bulek K; Liu C; Swaidani S; Wang L; Page RC; Gulen MF; Herjan T; Abbadi A; Qian W; Sun D; Lauer M; Hascall V; Misra S; Chance MR; Aronica M; Hamilton T; Li X. 2011. The inducible kinase IKKi is required for IL-17-dependent signaling associated with neutrophilia and pulmonary inflammation. Nat Immunol 12(9):844-52. [PubMed: 21822257]  [MGI Ref ID J:176466]

Chiang SH; Bazuine M; Lumeng CN; Geletka LM; Mowers J; White NM; Ma JT; Zhou J; Qi N; Westcott D; Delproposto JB; Blackwell TS; Yull FE; Saltiel AR. 2009. The protein kinase IKKepsilon regulates energy balance in obese mice. Cell 138(5):961-75. [PubMed: 19737522]  [MGI Ref ID J:153893]

Dai J; Shen DF; Bian ZY; Zhou H; Gan HW; Zong J; Deng W; Yuan Y; Li F; Wu QQ; Gao L; Zhang R; Ma ZG; Li HL; Tang QZ. 2013. IKKi deficiency promotes pressure overload-induced cardiac hypertrophy and fibrosis. PLoS One 8(1):e53412. [PubMed: 23349709]  [MGI Ref ID J:195693]

Jin J; Xiao Y; Chang JH; Yu J; Hu H; Starr R; Brittain GC; Chang M; Cheng X; Sun SC. 2012. The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-kappaB signaling. Nat Immunol 13(11):1101-9. [PubMed: 23023393]  [MGI Ref ID J:188560]

Ng SL; Friedman BA; Schmid S; Gertz J; Myers RM; Tenoever BR; Maniatis T. 2011. IkappaB kinase epsilon (IKK(epsilon)) regulates the balance between type I and type II interferon responses. Proc Natl Acad Sci U S A 108(52):21170-5. [PubMed: 22171011]  [MGI Ref ID J:180134]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   19-APR-08
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	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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Terms of Use

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