title: Prevalence and influence of cys407* Grm2 mutation in Hannover-derived Wistar rats: mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour.
abstract: Modulation of metabotropic glutamate 2 (mGlu2) receptor function has huge potential for treating psychiatric and neurological diseases. Development of drugs acting on mGlu2 receptors depends on the development and use of translatable animal models of disease. We report here a stop codon mutation at cysteine 407 in Grm2 (cys407*) that is common in some Wistar rats. Therefore, researchers in this field need to be aware of strains with this mutation. Our genotypic survey found widespread prevalence of the mutation in commercial Wistar strains, particularly those known as Han Wistar. Such Han Wistar rats are ideal for research into the separate roles of mGlu2 and mGlu3 receptors in CNS function. Previous investigations, unknowingly using such mGlu2 receptor-lacking rats, provide insights into the role of mGlu2 receptors in behaviour. The Grm2 mutant rats, which dominate some selectively bred lines, display characteristics of altered emotionality, impulsivity and risk-related behaviours and increased voluntary alcohol intake compared with their mGlu2 receptor-competent counterparts. In addition, the data further emphasize the potential therapeutic role of mGlu2 receptors in psychiatric and neurological disease, and indicate novel methods of studying the role of mGlu2 and mGlu3 receptors. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Wood
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Celine S
authors.initials: CS
authors.lastname: Nicolas
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Sun-Lim
authors.initials: SL
authors.lastname: Choi
authors.affiliation: Neuropharmacology, Addiction and Behaviour, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, 751 24 Uppsala, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Roman
authors.affiliation: Neuropharmacology, Addiction and Behaviour, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, 751 24 Uppsala, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Nylander
authors.affiliation: Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, Bellaterra, 08193 Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernandez-Teruel
authors.affiliation: Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, POB 30 00271 Helsinki, Finland.
authors.forename: Kalervo
authors.initials: K
authors.lastname: Kiianmaa
authors.affiliation: Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Bienkowski
authors.affiliation: Department of Behavioural and Molecular Neuroendocrinology, University of Regensburg, 93040 Regensburg, Germany.
authors.forename: Trynke R
authors.initials: TR
authors.lastname: de Jong
authors.affiliation: Neuroscience Institute, Section of Cagliari, National Research Council of Italy, I09042 Monserrato, CA, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Colombo
authors.affiliation: Janvier Labs, CS4105 Le Genest-Saint-Isle, F-53941 Saint-Berthevin, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Chastagnier
authors.affiliation: Eli Lilly Research Laboratories, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wafford
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.affiliation: Envigo, 8520 Allison Pointe Boulevard, Indianapolis IN 46250, USA.
authors.forename: Sheryl J
authors.initials: SJ
authors.lastname: Wildt
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
authors.forename: Becky L
authors.initials: BL
authors.lastname: Conway-Campbell
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Emma S J
authors.initials: ES
authors.lastname: Robinson
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK. Electronic address: david.lodge@bristol.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Lodge
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology; D000818:Animals; D003553:Cystine / Q000235:genetics*; D004644:Emotions / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics*; D009924:Organ Culture Techniques; D015995:Prevalence; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000235:genetics*; D012309:Risk-Taking; D013045:Species Specificity
chemical_list: D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D003553:Cystine
keywords: Alcohol preference; Anxiety; Emotionality; Grm2 mutation; Han Wistar rats; Metabotropic glutamate receptor; Selectively bred rats; Wistar rats; mGlu2