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Homozygous IKKepsilon knockout mouse as an animal model for influenza virus infection



Technology:
IKKepsilon (-/-) KO mice

Markets Addressed


The immune response to virus infection is a complex orchestration of both innate and adaptive immune events. Infected cells respond by initiating antiviral defenses on two levels: recruitment of specialized immune cells and establishment of a hostile cellular environment to slow virus replication and reduce viral load. The identification of genes that control viral replication at the site of infection and viral load may provide useful therapeutic targets for treating viral infections. Further, there remains an unmet medical need for new and effective therapeutic agents to treat viral infections.

Innovations and Advantages


Homozygous IKKepsilon (inhibitor of kappaB kinase epsilon) mutant mice are used as animal models for influenza virus infection. 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 interferon (IFN) signaling. These mice had an elevated viral load when compared to their control littermates. 7 days post infection, the lungs of the mutant mice display inflammatory infiltrate consisting of lymphocytes, macrophages, and neutrophils. The display of hypophosphorylated STAT1 protein was prevented. These IKKepsilon mutant mice may be useful in immunological studies involving IFN signaling and host responses to infection.

Additional Information


IKKepsilon (-/-) KO mice are available through Jackson Laboratory. Use of these mice by companies or for-profit entities requires a separate commercial license from Harvard University.

JAX 006908

Exons 4-6 of the targeted gene (inhibitor of kappaB kinase epsilon) were replaced with a PGK-neo cassette. Mice show a complete loss of the endogenous kinase function in lung, spleen, and embryonic fibroblasts.

Publication:
Multiple functions of the IKK-related kinase IKK-epsilon in interferon-mediated antiviral immunity. 2007. Science. 315(5816):1274-8.



Inventor(s):
    Maniatis, Thomas
    tenOever, Benjamin R.

Categories:
For further information, please contact:
Debra Peattie, Director of Business Development
(617) 495-3067
Reference Harvard Case #2807