# Functional Characterization of ASD-Associated EEF1A2 Mutations in Human Neurons

> **NIH NIH F30** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $44,889

## Abstract

Project Summary:
 Protein synthesis is a fundamental process in all living cells and is highly regulated to accommodate the
specific needs of each cell. Dysregulated protein synthesis has been demonstrated to underlie many of
syndromic forms of autism such as Fragile X syndrome (FXS) and Tuberous Sclerosis Complex (TSC), both of
which result from defects in genes that regulate protein synthesis. Moreover, mouse models of FXS and TSC
exhibit defective synaptic function, and ASD-like behaviors. Recent studies have shown that Eukaryotic
Elongation Factor 1A2 (EEF1A2), a protein responsible for GTP-dependent transport of aminoacyl-tRNAs to the
elongating ribosome, is mutated in patients with autism, intellectual disability and epilepsy. Elongation Factor 1A
has two isoforms, one that is ubiquitously expressed, EEF1A1, and another, EEF1A2 that is expressed only in
neurons and myocytes. It is unclear why another isoform is needed in these specific cells; however, it has been
found that EEF1A2 is critical for neuronal survival. The wasted mouse, a mouse model with a homozygous
deletion of mouse Eef1a2, has been found to exhibit neuron degeneration, tremors, loss of muscle bulk and gait
abnormalities after weaning. EEF1A2 has been also shown to bundle actin and microtubules independently of
translation, a process known to be critical for neuronal development and migration. This evidence suggests a
critical role played by EEF1A2 in neuronal development and function.
 This proposal aims to uncover how ASD-associated mutations in EEF1A2 results in deficits in neuronal
development and autism pathophysiology. Using human iPSC (induced pluripotent stems cells) derived neurons
as a model, the CRISPR-Cas9 system will be used to recapitulate patient mutations. These iPSCs will then be
differentiated into neurons using neurogenin-2, a master transcription factor capable of inducing differentiation
into excitatory neurons in under 2 weeks. Using this platform, the effect of ASD-associated mutations on neuronal
function will be studied. The first aim examines the effect of ASD-associated EEF1A2 mutations on protein
synthesis in neurons, given the central role that EEF1A2 plays in protein synthesis. Furthermore, the changes
to the translatome profile, elongation rate and translational efficiency in these cells will be identified. The second
aim will explore changes to neuronal morphology. function and development. After differentiation, induced
neurons with ASD-associated EEF1A2 mutations will be examined for altered morphology using
immunocytochemical analysis. During differentiation, live cell imaging will be used to track neurite growth and
the aberrant signaling pathways involved in actin dynamics and cytoskeletal regulation will be studied. Finally,
electrophysiology will used to assess synapse function and strength by measuring excitatory post synaptic
currents. The proposed research will advance our understanding of the role translation control plays in neuron...

## Key facts

- **NIH application ID:** 10476458
- **Project number:** 5F30HD103360-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Muhaned Mohamed
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $44,889
- **Award type:** 5
- **Project period:** 2020-09-04 → 2025-09-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476458

## Citation

> US National Institutes of Health, RePORTER application 10476458, Functional Characterization of ASD-Associated EEF1A2 Mutations in Human Neurons (5F30HD103360-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10476458. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*