Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee, USA.
Genes Brain Behav. 2020 Sep;19(7):e12654. doi: 10.1111/gbb.12654. Epub 2020 Apr 14.
Neurodevelopmental disorders are characterized by deficits in communication, cognition, attention, social behavior and/or motor control. Previous studies have pointed to the involvement of genes that regulate synaptic structure and function in the pathogenesis of these disorders. One such gene, GRM7, encodes the metabotropic glutamate receptor 7 (mGlu ), a G protein-coupled receptor that regulates presynaptic neurotransmitter release. Mutations and polymorphisms in GRM7 have been associated with neurodevelopmental disorders in clinical populations; however, limited preclinical studies have evaluated mGlu in the context of this specific disease class. Here, we show that the absence of mGlu in mice is sufficient to alter phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep. Moreover, Grm7 knockout mice exhibit an attenuated response to amphetamine. These findings provide rationale for further investigation of mGlu as a potential therapeutic target for neurodevelopmental disorders such as idiopathic autism, attention deficit hyperactivity disorder and Rett syndrome.
神经发育障碍的特征是在沟通、认知、注意力、社会行为和/或运动控制方面存在缺陷。先前的研究表明，调节突触结构和功能的基因参与了这些疾病的发病机制。GRM7 就是这样一个基因，它编码代谢型谷氨酸受体 7（mGlu7），一种调节突触前神经递质释放的 G 蛋白偶联受体。GRM7 中的突变和多态性与临床人群中的神经发育障碍有关；然而，有限的临床前研究评估了 mGlu7 在特定疾病类别中的作用。在这里，我们表明，在小鼠中缺乏 mGlu7 足以改变社会行为、联想学习、运动功能、癫痫和睡眠等领域的表型。此外，Grm7 基因敲除小鼠对安非他命的反应减弱。这些发现为进一步研究 mGlu7 作为神经发育障碍（如特发性自闭症、注意缺陷多动障碍和雷特综合征）的潜在治疗靶点提供了依据。
