Identifying the Molecular and Behavioral Basis of Cerebellar Dysfunction in TcMAC-21 and Dp16 Mouse Models of Down Syndrome

Date of Award

5-1-2025

Degree Name

M.S. in Biology

Department

Department of Biology

Advisor/Chair

Aaron Sathyanesan

Abstract

Down Syndrome (DS), a prevalent neurodevelopmental disorder, is caused by the triplication of chromosome 21 (Trisomy 21). This genetic anomaly leads to distinct cognitive and motor impairments, often linked to cerebellar dysfunction. Prior studies have reported cerebellar hypoplasia and a reduction in both Purkinje cells (PCs) and granule cells (GCs) in humans and mouse models of DS. Given the cerebellum’s crucial role in motor coordination, its abnormal development likely contributes to the motor deficits observed in individuals with DS. However, the extent to which altered synaptic input to PCs impacts motor deficits remains unclear. This study aims to investigate cerebellar cytoarchitecture using immunohistochemistry (IHC) and locomotor function using the ErasmusLadder in both TcMAC-21 and Dp16 mouse models of DS, compared to euploid controls. TcMAC-21 mice carry a cloned human chromosome 21, while Dp16 mice possess a duplication of the orthologous region on mouse chromosome 16. This study provides insight into genetic differences in DS models and their impact on phenotypes. Future research will further link cerebellar alterations to motor development, paving the way for potential therapies.

Keywords

Biology, Neurosciences

Rights Statement

Copyright 2025, author.

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