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Volume 11
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Article

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

by
Herwig P. Moll
1,
Julian Mohrherr
2,
Leander Blaas
2,3,
Monica Musteanu
2,4,
Patricia Stiedl
2,
Beatrice Grabner
2,
Katalin Zboray
2,5,
Margit König
6,
Dagmar Stoiber
2,7,
Thomas Rülicke
8,
Sabine Strehl
6,
Robert Eferl
9 and
Emilio Casanova
1,2,*
1
Department of Physiology, Center of Physiology and Pharmacology, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria
2
Ludwig Boltzmann Institute for Cancer Research (LBI-CR), 1090 Vienna, Austria
3
Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Novum, 14183 Huddinge, Sweden
4
CNIO (Spanish National Cancer Research Centre), E-28029 Madrid, Spain
5
Plant Protection Institute, Centre for Agricultural Research, Hungarian Academy of Sciences, 2462 Martonvásár, Hungary
6
Children’s Cancer Research Institute, St. Anna Kinderkrebsforschung, 1090 Vienna, Austria
7
Department of Pharmacology, Center of Physiology and Pharmacology, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria
8
Institute of Laboratory Animal, Science, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
9
Institute of Cancer Research, Medical University Vienna & Comprehensive Cancer Center (CCC), 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(9), 1226; https://doi.org/10.3390/cancers11091226
Submission received: 6 August 2019 / Accepted: 16 August 2019 / Published: 22 August 2019
(This article belongs to the Special Issue JAK-STAT Signalling Pathway in Cancer)
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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.
Keywords: bacterial artificial chromosome; recombineering; Cre/loxP; gene targeting; embryonic stem cells; liver steatosis bacterial artificial chromosome; recombineering; Cre/loxP; gene targeting; embryonic stem cells; liver steatosis

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MDPI and ACS Style

Moll, H.P.; Mohrherr, J.; Blaas, L.; Musteanu, M.; Stiedl, P.; Grabner, B.; Zboray, K.; König, M.; Stoiber, D.; Rülicke, T.; et al. A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions. Cancers 2019, 11, 1226. https://doi.org/10.3390/cancers11091226

AMA Style

Moll HP, Mohrherr J, Blaas L, Musteanu M, Stiedl P, Grabner B, Zboray K, König M, Stoiber D, Rülicke T, et al. A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions. Cancers. 2019; 11(9):1226. https://doi.org/10.3390/cancers11091226

Chicago/Turabian Style

Moll, Herwig P., Julian Mohrherr, Leander Blaas, Monica Musteanu, Patricia Stiedl, Beatrice Grabner, Katalin Zboray, Margit König, Dagmar Stoiber, Thomas Rülicke, and et al. 2019. "A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions" Cancers 11, no. 9: 1226. https://doi.org/10.3390/cancers11091226

APA Style

Moll, H. P., Mohrherr, J., Blaas, L., Musteanu, M., Stiedl, P., Grabner, B., Zboray, K., König, M., Stoiber, D., Rülicke, T., Strehl, S., Eferl, R., & Casanova, E. (2019). A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions. Cancers, 11(9), 1226. https://doi.org/10.3390/cancers11091226

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