# UNDERSTANDING THE CONSEQUENCES OF SLEEP LOSS IN AN AUTISM MOUSE MODEL

> **NIH NIH F99** · WASHINGTON STATE UNIVERSITY · 2024 · $49,974

## Abstract

PROJECT SUMMARY
Poor sleep is common in neurodevelopment disorders such as autism spectrum disorder (ASD), with up to
93% of ASD individuals reporting sleep problems. These problems worsen quality of life and core symptoms of
ASD and likely precede an ASD diagnosis, suggesting they start early in life. The potential adverse impact of
early life sleep disruption is supported by animal model studies showing long term functional consequences on
behavior. However, little is known about the underlying molecular consequences of sleep deprivation (SD)
early in life. Our recent work in wildtype mice demonstrates that the cortical transcriptional response to SD is
more prominent at postnatal day 24 (P24) with a preferential downregulation on the Wnt-singling pathway
compared to adulthood. Nevertheless, the transcriptional response and molecular mechanisms underlying the
adverse effects of SD early in life are poorly understood in the context of ASD. My overall goal is to understand
the detrimental consequences of sleep loss in neurodevelopmental disorders. Previous work in the lab showed
that mice carrying a mutation in the ASD gene Shank3 (Shank3∆C mice) are the only ASD mouse model that
replicates the clinical features of insomnia in ASD and show an abnormal transcriptional response to SD in
adults. In my graduate work, I used polysomnography in young Shank3∆C mice to show that sleep problems
are present and detectable at P24. In the F99 phase, I will investigate how this ASD mutation alters the impact
of SD on transcription at P24 using both bulk and single nuclear RNA sequencing. In addition, I will use
targeted quantitative proteomic for SHANK3 and -catenin to investigate the effects of Shank3∆C and SD on
canonical Wnt-signaling. Nuclear -catenin levels are a well-established marker of canonical Wnt-signaling
activation and SHANK3 has been shown to bind -catenin in the nucleus and inhibit its transcriptional activity.
My sponsor, Dr. Peixoto has an established track record analyzing transcriptomic response to SD in mouse
models and has establishes the Shank3∆C model for the study of sleep in ASD. My co-sponsor, Dr. Frank has
extensive experience in developmental neuroscience and has pioneered many of the studies characterizing
the role of sleep-in developmental synaptic plasticity. Additional members of my advisory committee, Dr Hicks
and Dr. Prasad are world experts on single-cell transcriptomics and proteomics. In the pre-doctoral F99 phase,
I will learn to use proteomic and transcriptomics approaches and advanced transcriptomic data analysis. In the
postdoctoral K00 phase, I will build upon these skills and use genetic mouse models to integrate circuit level
manipulation and multi-omics to better understand the consequences of sleep loss on behavior in
neurodevelopmental disorders. Overall, the proposed training will optimally position me to start an independent
research career at a leading neuroscience research institute and advance our unders...

## Key facts

- **NIH application ID:** 10930977
- **Project number:** 5F99NS135815-02
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Elizabeth Medina
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $49,974
- **Award type:** 5
- **Project period:** 2023-09-18 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930977

## Citation

> US National Institutes of Health, RePORTER application 10930977, UNDERSTANDING THE CONSEQUENCES OF SLEEP LOSS IN AN AUTISM MOUSE MODEL (5F99NS135815-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10930977. Licensed CC0.

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