# Developing an Astroglial Model for Fragile X Syndrome

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $434,385

## Abstract

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and
one of the main identified genetic causes of autism spectrum disorder. Our understanding
of neuropathophysiology of FXS is mainly gained from studies in the fmr1 null mouse
model. However, these studies don’t always translate to the human condition due to
species and possibly the mode of gene silencing in FXS. These limitations have been
recently circumvented by the advent of human induced pluripotent stem cells (hiPSCs),
and the generation of FXS patient-derived hiPSCs, which presents an opportunity for
studying the pathogenesis of FXS with unlimited human brain cells. Although astrocytes,
non-neuronal cells in the brain, have extensive roles in normal brain function, are
increasingly implicated in multiple brain disorders and express FMRP into adulthood, a
comprehensive understanding of the role of astrocytic FMRP in the pathogenesis of FXS
is still lacking. We will therefore develop a human cellular model of FXS by differentiating
astrocytes from control and FXS induced hiPSCs. In order to determine how FXS
astrocytes are impaired and how they impact formation and function of neural circuits, we
propose to create a humanized chimeric mouse model with hiPSCs. In Aim1 we will
examine how FXS astrocyte morphology, Ca2+ signaling and gene expression are
impaired in vivo. In Aim 2, we will determine the effect of FXS hIPSC-astrocytes on
neuronal structure and function. This work is expected to provide important knowledge
about the role of human specific astrocytes in FXS and has the potential to identify novel
therapeutic targets for FXS.

## Key facts

- **NIH application ID:** 10317618
- **Project number:** 1R21NS122157-01A1
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Anna Dunaevsky
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $434,385
- **Award type:** 1
- **Project period:** 2021-08-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317618

## Citation

> US National Institutes of Health, RePORTER application 10317618, Developing an Astroglial Model for Fragile X Syndrome (1R21NS122157-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10317618. Licensed CC0.

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