title: Targeted chemical-genetic regulation of protein stability in vivo.
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.
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Susana
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wolfgang
mesh_terms: D000818:Animals; D002262:Carboxy-Lyases / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D055550:Protein Stability / Q000187:drug effects; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D011506:Proteins; D054852:Small Molecule Libraries; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase