A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions

• Published in: Cancers Vol. 11; no. 9; p. 1226
• Main Authors: Moll, Herwig P, Mohrherr, Julian, Blaas, Leander, Musteanu, Monica, Stiedl, Patricia, Grabner, Beatrice, Zboray, Katalin, König, Margit, Stoiber, Dagmar, Rülicke, Thomas, Strehl, Sabine, Eferl, Robert, Casanova, Emilio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.08.2019; MDPI
• Subjects: Animal models; Artificial chromosomes; bacterial artificial chromosome; Cancer; Cell division; Cloning; Cre/loxP; Disease; Drug resistance; embryonic stem cells; Embryos; Fatty liver; gene targeting; Genes; Genomes; Genotype & phenotype; Hepatocytes; Kinases; Lethality; Liver; liver steatosis; Medicin och hälsovetenskap; Phenotypes; Physiology; recombineering; Stat3 protein; Stat5 protein; Steatosis; Stem cells; Toxicity; Transcription factors; Tumorigenesis; Tumors; bacterial artificial chromosome; gene targeting; liver steatosis; recombineering; Cre/loxP; embryonic stem cells
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers11091226

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. and 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 and we have developed a GEMM harboring a flox - allele ( mice) and generated mice lacking and in hepatocytes ( ). mice exhibited a marked reduction of STAT3, STAT5A and STAT5B proteins in the liver and developed steatosis, a phenotype that resembles mice lacking in hepatocytes. In addition, embryonic deletion of and ( mice) resulted in lethality, similar to mice. This data illustrates that mice are functional and can be used as a valuable tool to model the combined inhibition of and in tumorigenesis and other diseases.