Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Genetic variation in the metabotropic glutamate receptor 3 (GRM3, mGluR3) has been associated with schizophrenia, but the mechanism by which it confers risk is unknown. Previously, we reported the existence of a splice variant, GRM3Delta4, which has an exon 4 deletion and encodes a truncated form of the receptor that is expressed in brain. The aim of the present study was to determine whether expression of this splice variant is altered in individuals with schizophrenia and is affected by a risk genotype. We measured GRM3 and GRM3Delta4 transcripts in human dorsolateral prefrontal cortex (DLPFC) and hippocampus of the CBDB/NIMH collection ( approximately 70 controls, approximately 30 schizophrenia patients) and in the DLPFC of the Stanley Array Collection. Expression data of GRM3 mRNA in the DLPFC were inconsistent: GRM3 was increased in schizophrenia patients in the CBDB/NIMH collection, but not in the Stanley Array Collection. GRM3 expression did not change in the frontal cortex of rats treated chronically with haloperidol or clozapine. An exon 3 SNP previously associated with schizophrenia (rs2228595) predicted increased expression of the GRM3Delta4 splice variant. Our results suggest that rs2228595, or a neighboring SNP in linkage disequilibrium with it, may contribute to risk for schizophrenia by modulating GRM3 splicing.

Original publication




Journal article



Publication Date





2626 - 2634


Adult, Aged, Animals, Exons, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Predictive Value of Tests, Prefrontal Cortex, Protein Isoforms, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate, Risk Factors, Schizophrenia, Up-Regulation