Phuong (Harmony) Huynh

Major and Classification

Biological Sciences and Neuroscience and Minor in Chinese Language and Culture

Faculty Mentor

Chein-Ping Ko, Ph.D.


Dornsife College of Letters, Arts and Sciences

McNair Project

“Selective Vulnerability in Spinal Muscular Atrophy”

Project Abstract

Spinal muscular atrophy (SMA) is the leading genetic cause of death in childhood and is characterized by motor neuron loss and skeletal muscular deterioration. Our laboratory has shown that a subset of muscles in a mouse model of SMA (SMN Δ7) are vulnerable to denervation, such as branches 2 and 3 of the flexor digitorum brevis (FDB), whereas other muscles are resistant to denervation, such as branch 4 of the FDB. Yet, what contributes to selective vulnerability remains unknown. Recent studies suggest that synapse vulnerability to denervation in SMA may correlate to the types of neuromuscular junctions (NMJs), which can be categorized into two distinct classes: fast synapsing (FaSyn) and delayed synapsing (DeSyn). These NMJ phenotypes can be differentiated by their response to denervation. Specifically, following neuromuscular denervation, FaSyn muscles contain acetylcholine receptors (AChR) clusters that are compact and no Schwann cell (SC) sprouting occurs, whereas DeSyn muscles contain AChR that are dispersed and show SC sprouting. Selective vulnerability has been explored in a number of muscles, except in the flexor digitorum brevis (FDB). Whether or not branches 2-4 of the FDB are FaSyn or DeSyn muscles is an open question. To investigate if selective vulnerability of the FDB in SMN Δ7 mouse models is correlated to synapsing phenotype, we used neuromuscular denervation and α-bungarotoxin immunostaining to examine the structure of AChR and SC in branches 2-4 of the FDB after denervation. In this study, we observed AChR clustering and SC sprouting in all of the branches of the FDB, yet the synapsing phenotype could not be confirmed. Further work is necessary to consider if other intrinsic factors, such as time length in relation to nerve growth and the presence of agrin, help define FaSyn and De- Syn muscles and determine selective vulnerability in the FDB. Finding the answers to these questions will provide significant highlights to why certain muscles are more vulnerable to SMA.