Expression of a GRM3 splice variant is increased in the dorsolateral prefrontal cortex of individuals carrying a schizophrenia risk SNP

Leah J. Sartorius, Daniel Weinberger, Thomas Hyde, Paul J. Harrison, Joel Kleinman, Barbara K. Lipska

Research output: Contribution to journalArticle

Abstract

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, GRM3Δ4, 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 GRM3Δ4 transcripts in human dorsolateral prefrontal cortex (DLPFC) and hippocampus of the CBDB/NIMH collection (∼70 controls, ∼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 GRM3Δ4 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 languageEnglish (US)
Pages (from-to)2626-2634
Number of pages9
JournalNeuropsychopharmacology
Volume33
Issue number11
DOIs
StatePublished - Oct 2008
Externally publishedYes

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Prefrontal Cortex
Single Nucleotide Polymorphism
Schizophrenia
National Institute of Mental Health (U.S.)
Exons
Clozapine
Linkage Disequilibrium
Frontal Lobe
Haloperidol
Hippocampus
Genotype
Messenger RNA
Brain

Keywords

  • Bipolar disorder
  • Glutamate
  • Metabotropic
  • mGluR3
  • Neuroleptic
  • Post mortem

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Expression of a GRM3 splice variant is increased in the dorsolateral prefrontal cortex of individuals carrying a schizophrenia risk SNP. / Sartorius, Leah J.; Weinberger, Daniel; Hyde, Thomas; Harrison, Paul J.; Kleinman, Joel; Lipska, Barbara K.

In: Neuropsychopharmacology, Vol. 33, No. 11, 10.2008, p. 2626-2634.

Research output: Contribution to journalArticle

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