2026-08-29T14:25:02Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/83162024-11-29T16:27:14Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Moll, Herwig P author Mohrherr, Julian author Blaas, Leander author Musteanu, Mónica author Stiedl, Patricia author Grabner, Beatrice author Zboray, Katalin author König, Margit author Stoiber, Dagmar author Rülicke, Thomas author Strehl, Sabine author Eferl, Robert author Casanova, Emilio author 2019-08-22 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. Cancers (Basel). 2019;11(9). pii: E1226. 10.3390/cancers11091226 2072-6694 Cancers 31443474 http://hdl.handle.net/20.500.12105/8316 Cre/loxP bacterial artificial chromosome embryonic stem cells gene targeting liver steatosis recombineering A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions