A mouse model to assess STAT3 and STAT5A/B combined inhibition in health and disease conditions

Herwig P. Moll, Julian Mohrherr, Leander Blaas, Monica Musteanu, Patricia Stiedl, Beatrice Grabner, Katalin Zboray, Margit König, Dagmar Stoiber, Thomas Rülicke, Sabine Strehl, Robert Eferl, Emilio Casanova*

*Korrespondierende:r Autor:in für diese Arbeit

Publikation: Beitrag in Fachzeitschrift (peer-reviewed)Artikel in Fachzeitschrift

3 Zitate (Scopus)

Abstract

Genetically-engineered mouse models (GEMMs) lacking diseased-associated gene(s) globally or in a tissue-specific manner represent an attractive tool with which to assess the efficacy and toxicity of targeted pharmacological inhibitors. Stat3 and Stat5a/b transcription factors have been implicated in several pathophysiological conditions, and pharmacological inhibition of both transcription factors has been proposed to treat certain diseases, such as malignancies. To model combined inhibition of Stat3 and Stat5a/b we have developed a GEMM harboring a flox Stat3-Stat5a/b allele (Stat5/3loxP/loxP mice) and generated mice lacking Stat3 and Stat5a/b in hepatocytes (Stat5/3δhep/δhep). Stat5/3δhep/δhep mice exhibited a marked reduction of STAT3, STAT5A and STAT5B proteins in the liver and developed steatosis, a phenotype that resembles mice lacking Stat5a/b in hepatocytes. In addition, embryonic deletion of Stat3 and Stat5a/b (Stat5/3δ/δ mice) resulted in lethality, similar to Stat3δ/δ mice. This data illustrates that Stat5/3loxP/loxP mice are functional and can be used as a valuable tool to model the combined inhibition of Stat3 and Stat5a/b in tumorigenesis and other diseases.

OriginalspracheEnglisch
Aufsatznummer1226
FachzeitschriftCancers
Jahrgang11
Ausgabenummer9
DOIs
PublikationsstatusVeröffentlicht - Sept. 2019
Extern publiziertJa

ASJC Scopus Sachgebiete

  • Onkologie
  • Krebsforschung

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