Characterization of GPR139 and investigating its possible role in brain development

Abstract

G protein coupled receptors are a large family of cell surface receptors and are involved in a plethora of physiological functions from vision to various neuronal func tions. They have been a major target in the pharmaceutical industry and more than one third of currently available drugs target a GPCR. Although extensively studied, there are still 140 orphan GPCRs. GPR139 is an orphan GPCR in the rhodopsin fam ily and is primarily expressed in medial habenula. In addition to its cognate ligand, its function is still not known. At the time of the initiation of our study, the literature only suggested a possible role of GPR139 in neurological disorders such as ADHD and Alzheimer’s disease. Objective of this study is to investigate possible the role(s) of GPR139 in brain development via employing a Gpr139 knock-out mice model, and via in vivo ablation of Gpr139 in adult mice, and subjecting the animals to a set of behavioral experiments to measure the impact of deletion and ablation, respectively. In addition to animal experiments, various bioinformatic analyses were also performed to further characterize Gpr139. Our findings showed that Gpr139 is expressed differen tially in the brain tissue during embryonic development and its expression is most likely controlled by histone modifications and not DNA methylation. We also showed that ablation of GPR139 does not have any significant effects on spatial learning, locomotor activity, recognition memory and anxiety.