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

Mol Psychiatry. 2001 May;6(3):311-4. doi: 10.1038/sj.mp.4000848.

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 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.

MeSH terms

  • Case-Control Studies
  • Gene Frequency
  • Genome, Human
  • Humans
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / genetics*
  • Schizophrenia / genetics*
  • Scotland

Substances

  • GRM5 protein, human
  • Grm5 protein, mouse
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate

Associated data

  • GENBANK/AC022004
  • GENBANK/AC022005
  • GENBANK/AC022006
  • GENBANK/AC022014
  • GENBANK/AC024733
  • GENBANK/AC026078
  • GENBANK/AC026168
  • GENBANK/AC026201
  • GENBANK/AC027127
  • GENBANK/AC034188
  • GENBANK/AP000626
  • GENBANK/AP000653
  • GENBANK/AP001828