Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse

Background: Adhesion G protein‐coupled receptors (aGPCR) constitute a structurally and functionally diverse class of seven‐transmembrane receptor proteins. Although for some of the members important roles in immunology, neurology, as well as developmental biology have been suggested, most receptors have been poorly characterized. Results: We have studied evolution, expression, and function of an entire receptor group containing four uncharacterized aGPCR: Gpr110, Gpr111, Gpr115, and Gpr116. We show that the genomic loci of these four receptors are clustered tightly together in mouse and human genomes and that this cluster likely derives from a single common ancestor gene. Using transcriptional profiling on wild‐type and knockout/LacZ reporter knockin mice strains, we have obtained detailed expression maps that show ubiquitous expression of Gpr116, co‐expression of Gpr111 and Gpr115 in developing skin, and expression of Gpr110 in adult kidney. Loss of Gpr110, Gpr111, or Gpr115 function did not result in detectable defects, indicating that genes of this aGPCR group might function redundantly. Conclusions: The aGPCR cluster Gpr110, Gpr111, Gpr115, and Gpr116 developed from one common ancestor in vertebrates. Expression suggests a role in epithelia, and one can speculate about a possible redundant function of GPR111 and GPR115. Developmental Dynamics 241:1591–1602, 2012. © 2012 Wiley Periodicals, Inc. Key findings The cluster of four adhesion‐GPCR Gpr110, Gpr111, Gpr115, and Gpr116 is highly conserved in vertebrate evolution. Gpr116 is expressed ubiquitously in mice tissue, Gpr110 is strongly expressed in the renal pelvis. Gpr111 and Gpr115 are redundantly expressed in squamous epithelia in mice. Gpr111 and Gpr115 are expressed during embryonic development in the skin starting at embryonic day 12 with the formation of the basal layer of the skin.