Antisense knockouts: molecular scalpels for the dissection of signal transduction

The complexity of signal transduction is becoming increasingly apparent following the cloning of multiple families of receptors, G proteins, and effectors. Therefore, new tools are needed to assess the importance of particular subtypes in receptor-mediated signal transduction. One such tool is the use of antisense approaches to specifically 'knockout' particular G protein subtypes and then assess the functional consequences for receptor-signalling pathways. In this article by Paul Albert and Stephen Morris, various antisense approaches (including transfection of full-length cDNA) are discussed and compared for their specificity and efficiency. The antisense approach is argued to be applicable to a wide variety of signal-transduction systems, including G-protein-coupled receptor signalling, for analysis of the downstream events that dictate biological responsiveness.