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Updated: Feb 13, 2026

Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Aberrant mRNA splicing and impaired hippocampal neurogenesis in Grin2b mutant mice

Zohreh Farsi1, Ally Nicolella1, Sean K Simmons1,2

  • 1Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Iscience
|February 12, 2026
PubMed

Insights

Investigating a specific mutation in the Grin2b gene, crucial for NMDA receptors, revealed widespread gene expression changes and impaired neurogenesis in mice, offering insights into autism spectrum disorder (ASD) mechanisms.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • NMDA receptor dysfunction is linked to autism spectrum disorder (ASD) pathophysiology.
  • The Grin2b gene, encoding the GluN2B subunit, is a high-confidence ASD risk gene.

Purpose of the Study:

  • To investigate the effects of the ASD-linked C456Y mutation in Grin2b on brain function.
  • To explore the transcriptomic, splicing, and neurogenesis alterations in Grin2b mutant mice.

Main Methods:

  • Utilized heterozygous mouse mutants with the Grin2b C456Y mutation.
  • Conducted comprehensive transcriptomic analyses across brain regions and postnatal ages.
  • Examined splicing patterns and hippocampal neurogenesis.

Main Results:

  • Observed large-scale gene expression changes in oxidative phosphorylation and ribosome/translation pathways.
  • Discovered widespread splicing abnormalities and impaired hippocampal neurogenesis.
  • Found distinct transcriptomic patterns compared to Grin2a mutant mice.

Conclusions:

  • Grin2b plays a distinct role in brain development and function.
  • Alterations in Grin2b may contribute to neurodevelopmental disorders like ASD.
  • Findings highlight potential mechanisms involving energy metabolism and protein synthesis disruptions.
Keywords:
Molecular biologyNeuroscienceSystems biology

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