Targeted chemical-genetic regulation of protein stability in vivo

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Abstract

Loss- and gain-of-function transgenic models are powerful tools for understanding gene function in vivo but are limited in their ability to determine relative protein requirements. To determine cell-specific, temporal, or dose requirements of complex pathways, new methodology is needed. This is particularly important for deconstructing metabolic pathways that are highly interdependent and cross-regulated. We have combined mouse conditional transgenics and synthetic posttranslational protein stabilization to produce a broadly applicable strategy to regulate protein and pathway function in a cell-autonomous manner in vivo. Here, we show how a targeted chemical-genetic strategy can be used to alter fatty acid metabolism in a reombination and small-molecule-dependent manner in live behaving transgenic mice. This provides a practical, specific, and reversible means of manipulating metabolic pathways in adult mice to provide biological insight. © 2012 Elsevier Ltd.

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Rodriguez, S., & Wolfgang, M. J. (2012). Targeted chemical-genetic regulation of protein stability in vivo. Chemistry and Biology, 19(3), 391–398. https://doi.org/10.1016/j.chembiol.2011.12.022

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