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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Olney JW, Farber NB . Glutamate receptor dysfunction and schizophrenia Arch Gen Psychiatry 1995 52: 998–1007
Mohn AR, Gainetdinov RR, Caron MG, Koller BH . Mice with reduced NMDA receptor expression display behaviors related to schizophrenia Cell 1999 98: 427–436
Bordi F, Ugolini A . Group I metabotropic glutamate receptors: implications for brain diseases Prog Neurobiol 1999 59: 55–79
Geyer MA, Dulawa SC, Ralph RJ, Henry SA . Startle habituation and prepulse inhibition studies in mutant mice 55th Annual Conference of the Society of Biological Psychiatry, USA April 2000
Lu YM, Jia Z, Janus C, Henderson JT, Gerlai R, Wojtowicz JM et al. Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP J Neurosci 1997 17: 5196–5205
Ohnuma T, Augood SJ, Arai H, McKenna PJ, Emson PC . Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia Brain Res Mol Brain Res 1998 56: 207–217
St Clair D, Blackwood D, Muir W, Carothers A, Walker M, Spowart G et al. Association within a family of a balanced autosomal translocation with major mental illness Lancet 1990 336: 13–16
Blackwood D, Fordyce A, Walker M, StClair D, Porteous D, Muir W . Thirty-year follow-up of a family showing association of schizophrenia with a balanced translocation t(1:11)(q42,q14.3) Am J Med Genet 1998 81: 532
Devon RS, Porteous DJ . Physical mapping of a glutamate receptor gene in relation to a balanced translocation associated with schizophrenia in a large Scottish family Psychiatr Genet 1997 7: 165–169.
Devon RS, Evans KL, Maule JC, Christie S, Anderson S, Brown J et al. Novel transcribed sequences neighbouring a translocation breakpoint associated with schizophrenia Am J Med Genet 1997 74: 82–90
Millar JK, Brown J, Maule JC, Shibasaki Y, Christie S, Lawson D et al. A long-range restriction map across 3 Mb of the chromosome 11 breakpoint region of a translocation linked to schizophrenia: localization of the breakpoint and the search for neighbouring genes Psychiatr Genet 1998 8: 175–181
Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs Nucl Acids Res 1997 25: 3389–3402
Daggett LP, Sacaan AI, Akong M, Rao SP, Hess SD, Liaw C et al. Molecular and functional characterization of recombinant human metabotropic glutamate receptor subtype 5 Neuropharmacology 1995 34: 871–886
Underhill PA, Jin L, Lin AA, Mehdi SQ, Jenkins T, Vollrath D et al. Detection of numerous Y chromosome biallelic polymorphisms by denaturing high-performance liquid chromatography Genome Res 1997 7: 996–1005
O'Donovan MC, Oefner PJ, Roberts SC, Austin J, Hoogendoorn B, Guy C et al. Blind analysis of denaturing high-performance liquid chromatography as a tool for mutation detection Genomics 1998 52: 44–49
Smit AFA, Green P . RepeatMasker. URL: http://ftp.genome. washington.edu/RM/RepeatMasker.html
Cochrane WG . Some methods for strengthening the common chi-squared test Biometrics 1954 10: 417–451
Shaw SH, Kelly M, Smith AB, Shields G, Hopkins PJ, Loftus J et al. A genome-wide search for schizophrenia susceptibility genes Am J Med Genet 1998 81: 364–376
Coon H, Jensen S, Hoff M, Holik J, Plaetke R, Reimherr F et al. A genome-wide search for genes predisposing to manic-depression, assuming autosomal dominant inheritance Am J Hum Genet 1993 52: 1234–1249
Levinson DF, Mahtani MM, Nancarrow DJ, Brown DM, Kruglyak L, Kirby A et al. Genome scan of schizophrenia Am J Psychiatry 1998 155: 741–750
Maziade M, Raymond V, Cliche D, Fournier JP, Caron C, Garneau Y et al. Linkage results on 11Q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia Am J Med Genet 1995 60: 522–528
Wang ZW, Black D, Andreasen NC, Crowe RR . A linkage study of chromosome 11q in schizophrenia Arch Gen Psychiatry 1993 50: 212–216
Ewald H, Mors O, Flint T, Friedrich U, Eiberg H, Kruse TA . Linkage analysis between manicdepressive illness and markers on the long arm of chromosome 11 Am J Med Genet 1995 60: 386–392
Endicott J, Spitzer RL . A diagnostic interview: the schedule for affective disorders and schizophrenia Arch Gen Psychiatry 1978 35: 837–844
McGuffin P, Farmer AE, Harvey IH . A polydiagnostic application of operational criteria in studies of psychotic illness: development and reliability of the OPCRIT system Arch Gen Psychiatry 1991 48: 764–770
Huber CG, Oefner PJ, Bonn GK . High resolution liquid chromatography of oligonucleotides on nonporous alkylated styrene-divinylbenzene copolymers Anal Chem 1993 67: 578–585
Ewing B, Hillier L, Wendl M, Green P . Basecalling of automated sequencer traces using phred. I. Accuracy assessment Genome Res 1998 8: 175–185
Ewing B, Green P . Basecalling of automated sequencer traces using phred. II. Error probabilities Genome Res 1998 8: 186–194
Gordon D, Abajian C, Green P . Consed: a graphical tool for sequence finishing Genome Res 1998 8: 195–202
Minakami R, Katsuki F, Sugiyama H . A variant of metabotropic glutamate receptor subtype 5: an evolutionally conserved insertion with no termination codon Biochem Biophys Res Commun 1993 194: 622–627
Acknowledgements
We would like to thank Martin Taylor and Stephanie Le Hellard for their assistance with bioinformatics, Maura Walker for collating patient data and Dr Peng Lee Yap for his generous assistance in providing blood samples. This work was supported by the UK Medical Research Council and Organon Laboratories, Newhouse, Lanarkshire, UK. VM is funded by the John, Margaret, Alfred and Stewart Sim Fellowship through The Royal College of Physicians of Edinburgh.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Devon, R., Anderson, S., Teague, P. et al. The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia. Mol Psychiatry 6, 311–314 (2001). https://doi.org/10.1038/sj.mp.4000848
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.mp.4000848
Keywords
This article is cited by
-
Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors
Scientific Reports (2021)
-
Integrative analysis of genome-wide association studies identifies novel loci associated with neuropsychiatric disorders
Translational Psychiatry (2021)
-
mGluR5 hypofunction is integral to glutamatergic dysregulation in schizophrenia
Molecular Psychiatry (2020)
-
Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure
Translational Psychiatry (2019)
-
Touchscreen testing reveals clinically relevant cognitive abnormalities in a mouse model of schizophrenia lacking metabotropic glutamate receptor 5
Scientific Reports (2018)