Wood Christian M, Nicolas Celine S, Choi Sun-Lim, Roman Erika, Nylander Ingrid, Fernandez-Teruel Alberto, Kiianmaa Kalervo, Bienkowski Przemyslaw, de Jong Trynke R, Colombo Giancarlo, Chastagnier Denis, Wafford Keith A, Collingridge Graham L, Wildt Sheryl J, Conway-Campbell Becky L, Robinson Emma S J, Lodge David
School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK.
Neuropharmacology, Addiction and Behaviour, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, 751 24 Uppsala, Sweden.
Neuropharmacology. 2017 Mar 15;115:128-138. doi: 10.1016/j.neuropharm.2016.03.020. Epub 2016 Mar 14.
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'.
代谢型谷氨酸2（mGlu2）受体功能的调节在治疗精神疾病和神经疾病方面具有巨大潜力。作用于mGlu2受体的药物研发依赖于可转化疾病动物模型的开发与应用。我们在此报告，在某些Wistar大鼠中常见的Grm2基因第407位半胱氨酸处存在一个终止密码子突变（cys407*）。因此，该领域的研究人员需要留意携带此突变的品系。我们的基因型调查发现，该突变在商业Wistar品系中广泛存在，尤其是那些被称为Han Wistar的品系。此类Han Wistar大鼠对于研究mGlu2和mGlu3受体在中枢神经系统功能中的各自作用而言是理想的实验对象。先前的研究在不知情的情况下使用了此类缺乏mGlu2受体的大鼠，这为了解mGlu2受体在行为中的作用提供了线索。与具有mGlu2受体功能的同类大鼠相比，在一些选择性繁育品系中占主导地位的Grm2突变大鼠表现出情绪改变、冲动性和风险相关行为的特征，以及自愿酒精摄入量增加。此外，这些数据进一步强调了mGlu2受体在精神疾病和神经疾病中的潜在治疗作用，并指出了研究mGlu2和mGlu3受体作用的新方法。本文是名为“代谢型谷氨酸受体，五年之后”特刊的一部分。
