# GluN2D in Development and Disease

> **NIH NIH R03** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $73,025

## Abstract

PROJECT SUMMARY/ABSTRACT
NMDA receptors (NMDARs) are ligand-gated ion channels that are activated by glutamate, the
principle excitatory neurotransmitter of the brain. Missense mutations in NMDAR subunits are
associated with multiple neurodevelopmental disorders including autism, epilepsy and
morphological anomalies. Nevertheless, it is unclear how particular functional alterations
produce disease, especially as both gain and loss of function alleles have been identified with
the same disorders. This proposal uses zebrafish as a model to explore the developmental roles
of the understudied GluN2D subunit, which is associated with a severe neurological disorder,
Developmental and Epileptic Encephalopathy (DEE). Based on novel preliminary data that
shows NMDARs repress forebrain neurogenesis, we hypothesize that GluN2D dysfunction
alters early neurogenesis and the subsequent balance of excitatory and inhibitory neurons. We
propose two aims to test this premise. In Aim 1 we will determine the effects of complete loss of
GluN2D on neurogenesis to establish a foundation for understanding the pathogenic impacts of
GluN2D disease variants. In Aim 2 we will generate zebrafish models harboring DEE-associated
GluN2D variants to directly assess their effects on neurogenesis. This work will provide new
insights into the role of GluN2D in early development and establish a scalable strategy to
interrogate the pathogenic mechanisms produced disease associated NMDAR variants that
result in autism, epilepsy, and other neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 10526114
- **Project number:** 1R03HD107132-01A1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** HOWARD I SIROTKIN
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $73,025
- **Award type:** 1
- **Project period:** 2022-09-13 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526114

## Citation

> US National Institutes of Health, RePORTER application 10526114, GluN2D in Development and Disease (1R03HD107132-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10526114. Licensed CC0.

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