Regulators of G-protein signaling (RGS) proteins are important components of signal transduction pathways initiated through G-protein-coupled receptors (GPCRs). The RGS proteins have been proposed as novel drug targets since targeting GPCRs directly is the basis for the development of many therapeutics. Furthermore, evidence is mounting that RGS proteins may play a role in disease states such as schizophrenia, Parkinson’s Disease, hypertension, and addiction. Better understanding of the downstream side effects of RGS inhibition is necessary to determine its value as a drug target.
University of Michigan researchers have developed a mutant mouse line in which the inhibitory effects of RGS proteins on Galphai2 signaling, is prevented by a point mutation knocked-in to the mouse genomic Galphai2 locus. This mouse line can be used for target validation for RGS protein drug targets. The mice will permit the scientist to assess how inhibition of RGS action can facilitate physiological and pharmacological responses such as metabolic regulation, analgesic effects, and cardioprotection from ischemic injury.
Applications and Advantages
- Study of RGS signaling pathway.
- Target validation of RGS protein drugs.
- Overcomes the redundancy of RGS functions and reveals the total contribution of RGS regulation at the Galphai2 subunit.