| First Author | Farsi Z | Year | 2026 |
| Journal | iScience | Volume | 29 |
| Issue | 2 | Pages | 114700 |
| PubMed ID | 41675057 | Mgi Jnum | J:379188 |
| Mgi Id | MGI:8288117 | Doi | 10.1016/j.isci.2026.114700 |
| Citation | Farsi Z, et al. (2026) Aberrant mRNA splicing and impaired hippocampal neurogenesis in Grin2b mutant mice. iScience 29(2):114700 |
| abstractText | NMDA receptor dysfunction is implicated in the pathophysiology of autism spectrum disorder (ASD). Here, we investigated heterozygous mouse mutants carrying the ASD-linked C456Y mutation of Grin2b, a high-confidence ASD risk gene encoding the GluN2B subunit of NMDA receptors. Comprehensive transcriptomic analyses across brain regions and postnatal ages revealed large-scale gene expression changes, particularly in pathways related to oxidative phosphorylation and ribosome/translation, suggesting brain-wide alteration of energy metabolism and protein synthesis in Grin2b (+/C456Y) mice. We additionally discovered widespread splicing abnormalities and impaired hippocampal neurogenesis in Grin2b mutants. Interestingly, the underlying genes and the spatial and temporal patterns of transcriptomic changes in Grin2b (+/C456Y) mice differed substantially from those observed in mutant mice lacking Grin2a, encoding the GluN2A subunit of NMDA receptors and a schizophrenia risk gene. These findings underscore the distinct role of Grin2b in brain development and function and reveal potential mechanisms by which a lack of Grin2b may lead to neurodevelopmental disorders. |
