# Mechanisms of Down syndrome-associated swallowing dysfunction in mouse models

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $2,051,875

## Abstract

ABSTRACT
Down syndrome (DS), a genetic disorder, is associated with accelerated aging and high levels of swallowing
impairments (dysphagia). This is a critical concern given the increased survival of people with DS to older
ages, and the association of dysphagia, aspiration pneumonia, and death. Although dysphagia is a prominent
feature of DS, little is known about its age-related progression or the genetic mechanisms that underly its
etiology. There are significant knowledge gaps in DS research regarding how the extra copy of the human 21st
chromosome known to be present is driving DS phenotypes. The proposed research will address these gaps
through a collaboration between two laboratories with substantial expertise in translational animal models of
aging, DS, and dysphagia (Connor/Glass) and in the engineering of novel DS mouse models (Yu). The
overarching goals of the proposed work are to quantify effects of aging on DS-related dysphagia and to resolve
a current major uncertainty concerning the mechanisms underlying phenotypes in DS. There are two proposed
aims: (Aim 1) To test the hypothesis that dysphagia is exacerbated by aging in mouse models of DS by
quantifying swallowing function, tongue muscle alterations, changes in brainstem regions in mice of different
ages, and by performing additional analyses at the molecular and phenotypic levels; and (Aim 2) To quantify
the impacts of various components of a trisomy on swallowing function in DS in crucial behavioral and
biological variables. We will pursue the objective of Aim 2 by generating and analyzing a number of the novel
tailor-designed mouse models. This work is significant because it will define age-related changes in swallow
function in mouse models of DS using an ecologically valid assay (videofluoroscopy) that is also used clinically
in humans. Further, this work will introduce clarity regarding the impact of the critical elements of a trisomy on
DS-related dysphagia by using new mouse models thereby allowing us to unravel molecular contributors to
dysphagia in this context and to optimize translational precision. There are currently only limited compensatory
treatments for DS-associated dysphagia, and thus there is an urgent need to enhance our mechanistic
understanding of this clinical manifestation to support rational development of future therapeutic interventions.
This proposal is in response to NOT-OD-20-025, for the NIH INCLUDE Project on Down syndrome research.

## Key facts

- **NIH application ID:** 10444405
- **Project number:** 1R01DC019735-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** NADINE P CONNOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,051,875
- **Award type:** 1
- **Project period:** 2022-06-13 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444405

## Citation

> US National Institutes of Health, RePORTER application 10444405, Mechanisms of Down syndrome-associated swallowing dysfunction in mouse models (1R01DC019735-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10444405. Licensed CC0.

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