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Niswender Laboratory

Phenotypic profiling of mGlu knockout mice reveals new implications for neurodevelopmental disorders

AUTHORS

Fisher NMNicole M , Gould RWRobert W , Gogliotti RGRocco G , McDonald AJAnnalise J , Badivuku HHana , Chennareddy SSusmita , Buch ABAditi B , Moore AMAnnah M , Jenkins MTMatthew T , Robb WHW Hudson , Lindsley CWCraig W , Jones CKCarrie K , Conn PJP Jeffrey , Niswender CMColleen M . Genes, brain, and behavior. 2020 4 14; 19(7). e12654

ABSTRACT

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.

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