A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions
作者： Herwig P. Moll , Julian Mohrherr , Leander Blaas , Monica Musteanu , Patricia Stiedl
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摘要: 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 Stat5a/b transcription factors have been implicated several pathophysiological conditions, inhibition both has proposed treat certain diseases, such as malignancies. To model combined we developed GEMM harboring flox Stat3-Stat5a/b allele (Stat5/3loxP/loxP mice) generated mice hepatocytes (Stat5/3Δhep/Δhep). Stat5/3Δhep/Δhep exhibited marked reduction STAT3, STAT5A STAT5B proteins liver steatosis, phenotype that resembles hepatocytes. In addition, embryonic deletion (Stat5/3Δ/Δ resulted lethality, similar Stat3Δ/Δ mice. This data illustrates Stat5/3loxP/loxP are functional can be used valuable tumorigenesis other diseases.
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M Buchert, C J Burns, M Ernst, Targeting JAK kinase in solid tumors: emerging opportunities and challenges. Oncogene. ,vol. 35, pp. 939- 951 ,(2016) , 10.1038/ONC.2015.150
Thomas M. Magin, Jim McWhir, David W. Melton, A new mouse embryonic stem cell line with good germ line contribution and gene targeting frequency. Nucleic Acids Research. ,vol. 20, pp. 3795- 3796 ,(1992) , 10.1093/NAR/20.14.3795
Emilie Casanova, Sandra Fehsenfeld, Erich Greiner, Andrew Francis Stewart, Günther Schütz, Conditional mutagenesis of CamKIV Genesis. ,vol. 32, pp. 161- 164 ,(2002) , 10.1002/GENE.10034
Erin R. Cernkovich, Jianbei Deng, Michael C. Bond, Terry P. Combs, Joyce B. Harp, Adipose-Specific Disruption of Signal Transducer and Activator of Transcription 3 Increases Body Weight and Adiposity Endocrinology. ,vol. 149, pp. 1581- 1590 ,(2008) , 10.1210/EN.2007-1148
Amritha V Singireddy, Megan A Inglis, Wieteke A Zuure, Joon S Kim, Greg M Anderson, None, Neither signal transducer and activator of transcription 3 (STAT3) or STAT5 signaling pathways are required for leptin's effects on fertility in mice. Endocrinology. ,vol. 154, pp. 2434- 2445 ,(2013) , 10.1210/EN.2013-1109
Jörg J Jacoby, April Kalinowski, Mu-Gen Liu, Samuel S-M Zhang, Qian Gao, Gui-Xuan Chai, Lan Ji, Yoshiki Iwamoto, En Li, Michael Schneider, Kerry S Russell, Xin-Yuan Fu, Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure with advanced age Proceedings of the National Academy of Sciences of the United States of America. ,vol. 100, pp. 12929- 12934 ,(2003) , 10.1073/PNAS.2134694100
A. Kistner, M. Gossen, F. Zimmermann, J. Jerecic, C. Ullmer, H. Lubbert, H. Bujard, Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 10933- 10938 ,(1996) , 10.1073/PNAS.93.20.10933
Joep PP Muyrers, Youming Zhang, Giuseppe Testa, A Francis Stewart, Rapid modification of bacterial artificial chromosomes by ET-recombination. Nucleic Acids Research. ,vol. 27, pp. 1555- 1557 ,(1999) , 10.1093/NAR/27.6.1555
Giuseppe Testa, Youming Zhang, Kristina Vintersten, Vladimir Benes, W.W.M. Pim Pijnappel, Ian Chambers, Andrew J.H. Smith, Austin G. Smith, A. Francis Stewart, Engineering the mouse genome with bacterial artificial chromosomes to create multipurpose alleles Nature Biotechnology. ,vol. 21, pp. 443- 447 ,(2003) , 10.1038/NBT804
Yan-Ru Deng, Hong-Di Ma, Koichi Tsuneyama, Wei Yang, Yin-Hu Wang, Fang-Ting Lu, Cheng-Hai Liu, Ping Liu, Xiao-Song He, Anna Mae Diehl, M. Eric Gershwin, Zhe-Xiong Lian, STAT3-mediated attenuation of CCl4-induced mouse liver fibrosis by the protein kinase inhibitor sorafenib. Journal of Autoimmunity. ,vol. 46, pp. 25- 34 ,(2013) , 10.1016/J.JAUT.2013.07.008