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Transgenic Res (2012) 21:217224 DOI 10.1007/s11248-011-9519-5
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Generation of mice with a conditional Stat1 null allele
Barbara Wallner Nicole R. Leitner Raimund M. Vielnascher
Elisabeth Kernbauer Thomas Kolbe Marina Karaghiosoff
Thomas Rlicke Thomas Decker Mathias Mller
Received: 4 February 2011 / Accepted: 25 April 2011 / Published online: 7 May 2011 Springer Science+Business Media B.V. 2011
Abstract Interferons (IFNs) are key cytokines in the innate immune response that also bridge the gap to adaptive immunity. Signaling upon stimulation by IFN type I, II and III is mediated by the Jak-Stat pathway. STAT1 is activated by all three IFN receptor complexes and absence of STAT1 from mice increases their susceptibility to pathogens. In
addition, depending on the setting, STAT1 can act as tumor suppressor or oncogene. Here we report the generation and detailed functional characterization of a conditional Stat1 knockout mouse. We show the integrity of the conditional Stat1 locus and report successful in vivo deletion by means of a ubiquitous and a tissue-specic Cre recombinase. The conditional Stat1 null allele represents an important tool for identifying novel and cell-autonomous STAT1 functions in infection and cancer.
Keywords Stat1 Conditional knockout Cre
recombinase Interferon
Introduction
Signal transducer and activator of transcription (STAT) 1 is a latent cytoplasmic transcription factor that mediates diverse cellular functions ranging from proliferation and differentiation to apoptosis. As a result of alternative splicing, STAT1 exists as two isoforms: the full length STAT1a and the C-terminally truncated STAT1b. STAT1 is activated by a variety of growth factors and cytokines, most prominently by interferons (IFNs). Activation occurs mainly via phosphorylation on tyrosine 701 and serine 727. Activated STAT1 dimers translocate to the nucleus, where they bind specic DNA sequences and thereby inuence cellular gene expression
B. Wallner N. R. Leitner (&) R. M. Vielnascher
M. Karaghiosoff M. Mller
Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinarplatz 1, 1210 Vienna, Austriae-mail: [email protected]
E. Kernbauer T. Decker
Max F. Perutz Laboratories, Department of Genetics, Microbiology and Immunobiology, University of Vienna, Dr. Bohrgasse 9/4, 1030 Vienna, Austria
T. Kolbe T. Rlicke M. Mller (&)
University Center Biomodels Austria (BIAT), University of Veterinary Medicine, Veterinarplatz 1, 1210 Vienna, Austriae-mail: [email protected]
T. KolbeDepartment IFA-Tulln, Biotechnology in Animal Production, University of Natural Resources and Applied Life Sciences,...