Mills, A. A. (June 2001) Changing colors in mice: an inducible system that delivers. Genes & Development, 15 (12). pp. 1461-1467. ISSN 0890-9369
Abstract
Expression of exogenous genes in mammalian systems can be extremely informative for deciphering the function of an encoded protein or determining the role of a putative regulatory region. In many instances it is desirable or even essential to employ a system that has the ability to be controlled by the experimenter. For example, embryonic lethality that results from expression of an exogenous transgene or disruption of an endogenous gene can be problematic as it precludes examination of the phenotypic consequence in the organism under study. In these cases the use of an inducible gene expression system would be advantageous so that gene expression could be turned on or off at will. Inducible systems would not only be useful for analyzing the function of exogenous genes, but may also be implemented in gene disruption experiments or in gene therapy protocols in which a therapeutic gene is delivered. Many laboratories have designed systems that aim to achieve inducible gene expression. However, even the best laid plans often yield disappointing results in vivo. This is attributable to an incomplete understanding of regulatory mechanisms that orchestrate mammalian gene expression. Exacerbating this problem is the fact that bacterial or viral genes and regulatory elements that are often implemented in the scheme may be rendered nonfunctional in mammalian systems, further decreasing the chance of success and increasing the chance of frustration.
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