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Conditional ablation of TYK2 in immunity to viral infection and tumor surveillance

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Abstract

Tyrosine kinase 2 (TYK2) has a pivotal role in immunity to infection and tumor surveillance. It is associated with several cytokine receptor chains including type I interferon (IFN) receptor 1 (IFNAR1), interleukin- (IL-) 12 receptor beta 1 (IL-12Rb1) and IL-10R2. We have generated a mouse with a conditional Tyk2 null allele and proved integrity of the conditional Tyk2 locus. TYK2 was successfully removed by the use of ubiquitous and tissue-specific Cre-expressing mouse strains. Myeloid TYK2 was found to critically contribute to the defense against murine cytomegalovirus. Ubiquitous TYK2 ablation severely impaired tumor immunosurveillance, while deletion in myeloid, dendritic or T cells alone showed no effect. The conditional Tyk2 mouse strain will be instrumental to further dissect TYK2 functions in infection, inflammation and cancer.

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Acknowledgments

This work was supported by grants from the Austrian Science Fund (SFB-F28 and DK-W1212) to BS and MM and the Austrian Research Promotion Agency (GEN-AU III Austromouse) to MM and TR. We thank Claus Vogl for statistical support, Ursula Reichart and Barbara Wallner for support in mouse breeding and Doris Rigler, Carolin Hamann and Bettina Tutzer for technical assistance.

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Authors and Affiliations

  1. Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria

    Raimund M. Vielnascher, Eva Hainzl, Nicole R. Leitner, Michael Rammerstorfer, David Popp, Agnieszka Witalisz, Rita Rom, Marina Karaghiosoff, Simone Müller, Caroline Lassnig, Birgit Strobl & Mathias Müller

  2. University Center Biomodels Austria (BIAT), University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria

    Thomas Kolbe, Thomas Rülicke, Caroline Lassnig & Mathias Müller

  3. Institute of Laboratory Animal Science, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria

    Thomas Rülicke

  4. Department IFA-Tulln, Biotechnology in Animal Production, University of Natural Resources and Applied Life Sciences, 3430, Tulln, Austria

    Thomas Kolbe

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  1. Raimund M. Vielnascher
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  2. Eva Hainzl
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  3. Nicole R. Leitner
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  4. Michael Rammerstorfer
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  5. David Popp
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  6. Agnieszka Witalisz
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  7. Rita Rom
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  8. Marina Karaghiosoff
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  9. Thomas Kolbe
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  10. Simone Müller
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  11. Thomas Rülicke
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  12. Caroline Lassnig
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  13. Birgit Strobl
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  14. Mathias Müller
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Correspondence to Mathias Müller.

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Vielnascher, R.M., Hainzl, E., Leitner, N.R. et al. Conditional ablation of TYK2 in immunity to viral infection and tumor surveillance. Transgenic Res 23, 519–529 (2014). https://doi.org/10.1007/s11248-014-9795-y

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