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

• Published in: Molecular psychiatry Vol. 6; no. 3; pp. 311 - 314
• Main Authors: DEVON, R. S, ANDERSON, S, TEAGUE, P. W, MUIR, W. J, MURRAY, V, PELOSI, A. J, BLACKWOOD, D. H. R, PORTEOUS, D. J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.2001
• Subjects: Adult and adolescent clinical studies; Artificial chromosomes; Biological and medical sciences; Case-Control Studies; Channel gating; Child & adolescent psychiatry; Etiology; Gene Frequency; Genetic aspects; Genome, Human; Glutamic acid receptors (metabotropic); Hippocampal plasticity; Hippocampus; Humans; Medical sciences; Mental disorders; Microsatellite Repeats; Molecular Sequence Data; Mutation; N-Methyl-D-aspartic acid; Neuroplasticity; Neurotransmitter receptors; Neurotransmitters; Physiological aspects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Psychosis; Pyramidal cells; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate - genetics; Risk factors; Schizophrenia; Schizophrenia - genetics; Scotland; Sensorimotor gating; Synaptic plasticity; γ-Aminobutyric acid; Scotland; United Kingdom; Psychosis; Human; Schizophrenia; Glutamate receptor; Metabotropic receptor; Etiology
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4000848

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 schizophrenia and in another, a key rôle for this gene in the modulation of hippocampal NMDA-dependent synaptic plasticity. In humans, GRM5 levels are increased in certain pyramidal cell neurons in schizophrenics vs controls.(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). 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.