Phenotypic profiling of mGlu7 overexpressing mice and its implications for neurodevelopmental disorders such as Rett syndrome
Abstract
Neurodevelopmental disorders (NDDs) 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 (mGlu7), a G protein‐coupled receptor that regulates presynaptic neurotransmitter release. Mutations and polymorphisms in GRM7 have been associated with (NDDs) in clinical populations; however, limited preclinical studies have evaluated mGlu7 in the context of this specific disease class. Rett syndrome (RTT) is an NDD caused by mutations in the Methyl‐CpG Binding Protein 2 (MECP2) gene. The cognitive deficits seen in RTT model mice have been previously correlated with a deficit in long‐term potentiation (LTP) at Schaffer collateral‐CA1 (SC‐CA1) synapses in the hippocampus. mGlu7 is abundantly expressed presynaptically at SC‐CA1 synapses and its role in the regulation of GABA release is imperative for the induction of LTP. Previous studies from our lab have shown that mGlu7expression is reduced in autopsy samples from patients diagnosed with RTT and in mouse models of RTT. Our lab has also shown that abnormal phenotypes in RTT mice can be corrected with mGlu7 positive allosteric modulators (PAMs). Despite the beneficial effects of mGlu7 potentiation, it is important to understand how an increase in mGlu7expression affects phenotypes seen in NDDs like Rett syndrome.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 01, 2022
- Source ID
- 10.1096/fasebj.2022.36.s1.0r517
Entities
People
- Aditi Buch
- Colleen Niswender
- Geanne Frietas
- Kelly Weiss
- Nicole M Fisher
- Rocco Gogliotti
- Sheryl Vermudez
Organizations
- Congressionally Directed Medical Research Programs
- Loyola University Chicago
- Vanderbilt University