Transgenic Research

, Volume 23, Issue 3, pp 519–529 | Cite as

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

  • Raimund M. Vielnascher
  • Eva Hainzl
  • Nicole R. Leitner
  • Michael Rammerstorfer
  • David Popp
  • Agnieszka Witalisz
  • Rita Rom
  • Marina Karaghiosoff
  • Thomas Kolbe
  • Simone Müller
  • Thomas Rülicke
  • Caroline Lassnig
  • Birgit Strobl
  • Mathias Müller
Original Paper

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.

Keywords

Janus kinase JAK Tyrosine kinase 2 Conditional knockout Tumor transplant MCMV MC38 

Notes

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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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Raimund M. Vielnascher
    • 1
  • Eva Hainzl
    • 1
  • Nicole R. Leitner
    • 1
  • Michael Rammerstorfer
    • 1
  • David Popp
    • 1
  • Agnieszka Witalisz
    • 1
  • Rita Rom
    • 1
  • Marina Karaghiosoff
    • 1
  • Thomas Kolbe
    • 2
    • 4
  • Simone Müller
    • 1
  • Thomas Rülicke
    • 2
    • 3
  • Caroline Lassnig
    • 1
    • 2
  • Birgit Strobl
    • 1
  • Mathias Müller
    • 1
    • 2
  1. 1.Institute of Animal Breeding and GeneticsUniversity of Veterinary MedicineViennaAustria
  2. 2.University Center Biomodels Austria (BIAT)University of Veterinary MedicineViennaAustria
  3. 3.Institute of Laboratory Animal ScienceUniversity of Veterinary MedicineViennaAustria
  4. 4.Department IFA-Tulln, Biotechnology in Animal ProductionUniversity of Natural Resources and Applied Life SciencesTullnAustria

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