Grm5, encoding metabotropic glutamate receptor 5 (mGluR5), belongs to the family of G protein-coupled receptors. These receptors are obligate dimers, having a large extracellular ligand-binding domain linked to the 7-transmembrane domain via a cysteine-rich domain. mGluR5 is involved in regulating integrative brain function and synaptic transmission, with its aberrant signaling contributing to synaptic failure, a key pathophysiological mechanism in diseases like Alzheimer's disease [1,4].

Genetic disruption of Grm5 in mice (homozygous or heterozygous null mutations) causes complex alterations in motor activity, anxiety, and social behaviors. Digging and marble burying behaviors were almost completely abolished in mGluR5 knockout mice, while self-grooming was unaltered. Social interaction was impaired in knockout but not heterozygous mice. In tests of locomotor activity and anxiety-related behaviors, knockout mice showed hyperactivity in the open-field test and hypoactivity in the elevated zero-maze test. Also, Grm5 expression is not required for the oncogenic role of Grm1 in melanocytes, as TGM mice (homozygote knockouts for Grm5 and carrying the TG transgene) develop tumors similar to TG-3 mice [2,3].

In conclusion, Grm5 plays a crucial role in motor and social behaviors, as well as in potential disease-related processes such as melanoma development and cognitive-impairment-associated synaptic function. Mouse models with Grm5 gene knockout have been instrumental in revealing these functions, providing insights into the role of Grm5 in specific biological processes and disease conditions.

References:

1. Krishna Kumar, Kaavya, Wang, Haoqing, Habrian, Chris, Isacoff, Ehud Y, Kobilka, Brian K. 2024. Stepwise activation of a metabotropic glutamate receptor. In Nature, 629, 951-956. doi:10.1038/s41586-024-07327-x. https://pubmed.ncbi.nlm.nih.gov/38632403/

2. Marín, Yarí E, Namkoong, Jin, Shin, Seung-Shick, White, Eileen, Chen, Suzie. . Grm5 expression is not required for the oncogenic role of Grm1 in melanocytes. In Neuropharmacology, 49 Suppl 1, 70-9. doi:. https://pubmed.ncbi.nlm.nih.gov/16040064/

3. Xu, Jian, Marshall, John J, Kraniotis, Stephen, Zhu, Yongling, Contractor, Anis. 2021. Genetic disruption of Grm5 causes complex alterations in motor activity, anxiety and social behaviors. In Behavioural brain research, 411, 113378. doi:10.1016/j.bbr.2021.113378. https://pubmed.ncbi.nlm.nih.gov/34029630/

4. Wang, Jie, Huang, Qi, He, Kun, Li, Binying, Xie, Fang. 2024. Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment. In Alzheimer's & dementia : the journal of the Alzheimer's Association, 20, 3876-3888. doi:10.1002/alz.13817. https://pubmed.ncbi.nlm.nih.gov/38634334/