The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia

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Abstract
The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been implicated in the aetiology of schizophrenia as they modulate the NMDA response and that of other neurotransmitters including dopamine and GABA.1–3 Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study, a sensorimotor gating deficit characteristic of schizophrenia4 and in another, a key rôle for this gene in the modulation of hippocampal NMDA-dependent synaptic plasticity.5 In humans, GRM5 levels are increased in certain pyramidal cell neurons in schizophrenics vscontrols.6 Finally, GRM5 has been mapped to 11q14, neighbouring a translocation that segregates with schizophrenia and related psychoses in a large Scottish family, F23 (MLOD score 6.0).7,8 We determined the intron/exon structure of GRM5 and identified a novel intragenic microsatellite. A case-control association study identified a significant difference in allele frequency distribution between schizophrenics and controls (P = 0.04). This is suggestive of involvement of the GRM5 gene in schizophrenia in this population.