Expression map of 78 brain-expressed mouse orphan GPCRs provides a translational resource for neuropsychiatric research

Abstract

Orphan G-protein-coupled receptors (oGPCRs) possess untapped potential for drug discovery. In the brain, oGPCRs are generally expressed at low abundance and their function is understudied. Expression profiling is an essential step to position oGPCRs in brain function and disease, however public databases provide only partial information. Here, we fine-map expression of 78 brain-oGPCRs in the mouse, using customized probes in both standard and supersensitive in situ hybridization. Images are available at http://ogpcr-neuromap.douglas.qc.ca. This searchable database contains over 8000 coronal brain sections across 1350 slides, providing the first public mapping resource dedicated to oGPCRs. Analysis with public mouse (60 oGPCRs) and human (56 oGPCRs) genome-wide datasets identifies 25 oGPCRs with potential to address emotional and/or cognitive dimensions of psychiatric conditions. We probe their expression in postmortem human brains using nanoString, and included data in the resource. Correlating human with mouse datasets reveals excellent suitability of mouse models for oGPCRs in neuropsychiatric research.