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

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• 作者：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)
  
• 关键词：Janus kinase ; JAK ; Tyrosine kinase 2 ; Conditional knockout ; Tumor transplant ; MCMV ; MC38
• 刊名：Transgenic Research
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：23
• 期：3
• 页码：519-529
• 全文大小：
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• 作者单位：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. Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterin?rplatz 1, 1210, Vienna, Austria
  2. University Center Biomodels Austria (BIAT), University of Veterinary Medicine, Veterin?rplatz 1, 1210, Vienna, Austria
  4. Department IFA-Tulln, Biotechnology in Animal Production, University of Natural Resources and Applied Life Sciences, 3430, Tulln, Austria
  3. Institute of Laboratory Animal Science, University of Veterinary Medicine, Veterin?rplatz 1, 1210, Vienna, Austria
  
• ISSN：1573-9368

文摘

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.