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

First Author  Moll HP Year  2019
Journal  Cancers (Basel) Volume  11
Issue  9 PubMed ID  31443474
Mgi Jnum  J:344226 Mgi Id  MGI:7572663
Doi  10.3390/cancers11091226 Citation  Moll HP, et al. (2019) A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions. Cancers (Basel) 11(9)
abstractText  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 (Stat5/3(loxP/loxP) mice) and generated mice lacking Stat3 and Stat5a/b in hepatocytes (Stat5/3(Deltahep)(/Deltahep)). Stat5/3(Deltahep/Deltahep) 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 (Stat5/3(Delta)(/Delta) mice) resulted in lethality, similar to Stat3(Delta)(/Delta) mice. This data illustrates that Stat5/3(loxP/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.
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