Grin3b-KO Mouse

Grin3b, which encodes the GluN3B subunit of the N-methyl-D-aspartate (NMDA) receptor, is a crucial gene. The NMDA receptor is a glutamate-gated ionotropic cation channel, and many forms of synaptic plasticity rely on calcium ion influx through it. Thus, Grin3b is involved in important neural signal-transduction pathways and is of great significance for normal brain function [1].

In a family with a strong history of psychotic disorders, a frameshift mutation (rs10666583) in the Grin3B gene was found in all family members with a psychotic disorder but not in healthy relatives. This mutation degrades the S1/S2 glycine-binding domain of the GluN3B subunit, affecting the channel pore's calcium-ion permeability and potentially causing impaired NMDA receptor function, suggesting it could be a risk factor for psychotic disorders [1]. Additionally, in a transcriptome-wide association study, GRIN3B blood mRNA levels were associated with chronic vs. resilient post-trauma symptom trajectories, and genetic variants regulating its mRNA blood expression levels were identified, indicating its potential role in the manifestation of PTSD [2].

In conclusion, Grin3b is essential for the normal function of the NMDA receptor and synaptic plasticity. Studies on genetic mutations in families with psychotic disorders and post-trauma symptom trajectories in individuals suggest that Grin3b may play a role in the pathogenesis of psychotic disorders and PTSD, providing valuable insights into these complex neuropsychiatric conditions.

References:

1. Hornig, Tobias, Grüning, Björn, Kundu, Kousik, Biber, Knut, Normann, Claus. 2017. GRIN3B missense mutation as an inherited risk factor for schizophrenia: whole-exome sequencing in a family with a familiar history of psychotic disorders. In Genetics research, 99, e1. doi:10.1017/S0016672316000148. https://pubmed.ncbi.nlm.nih.gov/28132660/

2. Lori, Adriana, Schultebraucks, Katharina, Galatzer-Levy, Isaac, Wingo, Aliza P, Ressler, Kerry J. 2021. Transcriptome-wide association study of post-trauma symptom trajectories identified GRIN3B as a potential biomarker for PTSD development. In Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 46, 1811-1820. doi:10.1038/s41386-021-01073-8. https://pubmed.ncbi.nlm.nih.gov/34188182/