Tongue maturation deficits in a mouse model of Down syndrome

University Of Wisconsin-Madison, Madison WI

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Abstract

Abstract Atypical and delayed oromotor development is a well-known clinical aspect of Down syndrome (DS) and contributes to devastating challenges in speech, feeding, and swallowing. These challenges can affect the majority of individuals with DS, with profound consequences for quality of life and health. The tongue and brainstem are both complex systems that undergo rapid changes during early postnatal development and are critical for speech and swallowing. However, the central and peripheral changes occurring in early childhood that permit postnatal expansion in movement and function of the tongue are poorly understood in typical development and in DS. This proposal is for an administrative supplement to the INCLUDE-funded parent grant, “Tongue maturation deficits in a mouse model of Down syndrome”, which tests the central hypothesis that DS is associated with developmental delays in maturation of the tongue neuromuscular system. The parent grant uses the Ts65Dn mouse model of DS exclusively to generate normative data for the study of tongue and brainstem maturation at early postnatal ages and will determine how DS impacts lingual development. This is achieved through behavioral and immunofluorescence studies of tongue muscles and brainstem. However, new animal models of DS with superior genetic verisimilitude to DS have now become available. The proposed supplement work will expand a key subset of the parent grant goals to incorporate the new Ts66Yah mouse model of DS (Supplement Aim 1a). This supplement aim will further the science underlying both typical and delayed lingual maturation. As such, this work will provide basic knowledge for future efforts to develop biologically based approaches for successful resolution of pediatric oromotor disorders that impact children with DS. These goals will establish an experimental framework to advance biologically informed treatments for developmental speech, feeding, and swallowing disorders. This application addresses the NIH INCLUDE Component 1: Targeted high risk – high reward basic science studies in areas highly relevant to DS.