TY - JOUR
T1 - Targeted chemical-genetic regulation of protein stability in vivo
AU - Rodriguez, Susana
AU - Wolfgang, Michael J.
N1 - Funding Information:
We thank T.L. Wandless (Stanford University) and E. Provost (Johns Hopkins University) for critical reagents. This work was supported in part by the American Heart Association (SDG2310008 to M.J.W.) and NIH NINDS (NS072241 to M.J.W.).
PY - 2012/3/23
Y1 - 2012/3/23
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2011.12.022
DO - 10.1016/j.chembiol.2011.12.022
M3 - Article
C2 - 22444594
AN - SCOPUS:84858982859
VL - 19
SP - 391
EP - 398
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 3
ER -