>

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

Authors

Fisher NM Nicole M , Gould RW Robert W , Gogliotti RG Rocco G , McDonald AJ Annalise J , Badivuku H Hana , Chennareddy S Susmita , Buch AB Aditi B , Moore AM Annah M , Jenkins MT Matthew T , Robb WH W Hudson , Lindsley CW Craig W , Jones CK Carrie K , Conn PJ P Jeffrey , Niswender CM Colleen 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.

Tags: 2020