Abstract
Inducible gene expression systems are favored over stable expression systems in a wide variety of basic and applied research areas, including functional genomics, gene therapy, tissue engineering, biopharmaceutical protein production and drug discovery. This is because they are mostly reversible and thus more flexible to use. Furthermore, compared to constitutive expression, they generally exhibit a higher efficiency and have fewer side effects, such as cell death and delayed growth or development. Empowered by decades of development of inducible gene expression systems, researchers can now efficiently activate or suppress any gene, temporarily and quantitively at will, depending on experimental requirements and designs. Here, we review a number of most commonly used mammalian inducible expression systems and provide basic standards and criteria for the selection of the most suitable one.
Highlights
Classic genetic studies are based on correlating genetic alterations with the resulting phenotypes.Several important signaling pathways, including mTOR [1,2], apoptosis [3], autophagy [4] and Hippo [5,6]pathways, have been discovered by classic genetics
Even though a chimeric lacR-VP16 has been described to activate a minimal promoter almost 1000-fold at elevated temperatures in the presence of isopropyl β-D-thiogalactopyranoside (IPTG) [20], the temperature dependence and the inherent IPTG-related problems were found to limit the usability of this approach
Due to the immunosuppressive and the cell cycle inhibitory effect of FK506 and rapamycin [48], a new synthetic compound, FKCsA, which is a heterodimer of FK506 and cyclosporin A, was developed and was shown to exhibit neither toxicity nor immunosuppressive effects [53]
Summary
Classic genetic studies are based on correlating genetic alterations with the resulting phenotypes. The ability to switch the gene expression on and off or to modulate the level of gene expression in a quantitative and temporal way can preferentially reveal the direct consequence of a certain genetic change and provide an additional filter to exclude other side- and off-target effects This is especially beneficial when working with mammalian cells that are maintained and controlled by highly intricate genetic networks. Metallothionein promoter that originates from the equine kidney is regulated by heavy metals and by hypoxia, oxidative stress, and hormones, making it inappropriate for studies involving these biological processes [16,17,18] To overcome these drawbacks, discoveries of bacterial operons have inspired scientists to transfer these prokaryotic genetic elements into mammalian cells. These developments and recent progress in the field are discussed below
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