Prevalence and influence of cys407 Grm2 mutation in Hannover-derived Wistar rats: mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour
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...
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| Published in | Neuropharmacology Vol. 115; pp. 128 - 138 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
15.03.2017
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| Subjects | |
| Online Access | Get full text |
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| 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’.
•Discovery of cys407* mutation in Grm2 of Wistar rats.•High prevalence in Han Wistar sub-strains.•Grm2 mutation linked with alcohol-preferring rats.•Grm2 mutation linked with changes in risk taking and emotional behaviour. |
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| AbstractList | 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'.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'. 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’. •Discovery of cys407* mutation in Grm2 of Wistar rats.•High prevalence in Han Wistar sub-strains.•Grm2 mutation linked with alcohol-preferring rats.•Grm2 mutation linked with changes in risk taking and emotional behaviour. 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. 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'. |
| Author | Nylander, Ingrid Robinson, Emma S.J. Wood, Christian M. Choi, Sun-Lim Bienkowski, Przemyslaw Colombo, Giancarlo Lodge, David Nicolas, Celine S. Wafford, Keith A. Chastagnier, Denis Roman, Erika de Jong, Trynke R. Collingridge, Graham L. Fernandez-Teruel, Alberto Conway-Campbell, Becky L. Kiianmaa, Kalervo Wildt, Sheryl J. |
| Author_xml | – sequence: 1 givenname: Christian M. orcidid: 0000-0003-1267-5032 surname: Wood fullname: Wood, Christian M. organization: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK – sequence: 2 givenname: Celine S. surname: Nicolas fullname: Nicolas, Celine S. organization: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK – sequence: 3 givenname: Sun-Lim surname: Choi fullname: Choi, Sun-Lim organization: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK – sequence: 4 givenname: Erika surname: Roman fullname: Roman, Erika organization: Neuropharmacology, Addiction and Behaviour, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, 751 24 Uppsala, Sweden – sequence: 5 givenname: Ingrid surname: Nylander fullname: Nylander, Ingrid organization: Neuropharmacology, Addiction and Behaviour, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, 751 24 Uppsala, Sweden – sequence: 6 givenname: Alberto surname: Fernandez-Teruel fullname: Fernandez-Teruel, Alberto organization: Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, Bellaterra, 08193 Barcelona, Spain – sequence: 7 givenname: Kalervo surname: Kiianmaa fullname: Kiianmaa, Kalervo organization: Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, POB 30 00271 Helsinki, Finland – sequence: 8 givenname: Przemyslaw surname: Bienkowski fullname: Bienkowski, Przemyslaw organization: Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland – sequence: 9 givenname: Trynke R. surname: de Jong fullname: de Jong, Trynke R. organization: Department of Behavioural and Molecular Neuroendocrinology, University of Regensburg, 93040 Regensburg, Germany – sequence: 10 givenname: Giancarlo surname: Colombo fullname: Colombo, Giancarlo organization: Neuroscience Institute, Section of Cagliari, National Research Council of Italy, I09042 Monserrato, CA, Italy – sequence: 11 givenname: Denis surname: Chastagnier fullname: Chastagnier, Denis organization: Janvier Labs, CS4105 Le Genest-Saint-Isle, F-53941 Saint-Berthevin, France – sequence: 12 givenname: Keith A. surname: Wafford fullname: Wafford, Keith A. organization: Eli Lilly Research Laboratories, Windlesham, Surrey GU20 6PH, UK – sequence: 13 givenname: Graham L. surname: Collingridge fullname: Collingridge, Graham L. organization: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK – sequence: 14 givenname: Sheryl J. surname: Wildt fullname: Wildt, Sheryl J. organization: Envigo, 8520 Allison Pointe Boulevard, Indianapolis IN 46250, USA – sequence: 15 givenname: Becky L. surname: Conway-Campbell fullname: Conway-Campbell, Becky L. organization: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK – sequence: 16 givenname: Emma S.J. surname: Robinson fullname: Robinson, Emma S.J. organization: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK – sequence: 17 givenname: David surname: Lodge fullname: Lodge, David email: david.lodge@bristol.ac.uk organization: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26987983$$D View this record in MEDLINE/PubMed https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-318629$$DView record from Swedish Publication Index |
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| Keywords | Selectively bred rats Wistar rats Emotionality Han Wistar rats Alcohol preference Grm2 mutation Anxiety Metabotropic glutamate receptor mGlu2 RGD mGlu2 receptor |
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| SubjectTerms | Alcohol Drinking - genetics Alcohol Drinking - psychology Alcohol preference Animals Anxiety Cystine - genetics Emotionality Emotions - physiology Grm2 mutation Han Wistar rats Hippocampus - physiology Metabotropic glutamate receptor mGlu2 Mice, Knockout Mutation - genetics Organ Culture Techniques Prevalence Rats Rats, Wistar Receptors, Metabotropic Glutamate - deficiency Receptors, Metabotropic Glutamate - genetics Risk-Taking Selectively bred rats Species Specificity Wistar rats |
| 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 |
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