Date of Award




Document Type

Master's Thesis

Degree Name

Master of Science (MS)


Department of Biological Sciences

Content Description

1 online resource (iv, 65 pages) : illustrations (some color)

Dissertation/Thesis Chair

Thomas Begley

Committee Members

Andrew Berglund, Gabriele Fuchs


Myotonia atrophica, RNA editing, Mitochondrial pathology, Fibroblasts

Subject Categories

Cell Biology | Molecular Biology | Neuroscience and Neurobiology


Myotonic dystrophy (DM), the most common form of muscular dystrophy, is a neuromuscular disease caused by microsatellite repeat expansions. It can represent a multi-systemic autosomal dominant disease with DM1 and DM2 subtypes. A cytosine-thymine-guanine (CTG) triplet repeat in the 3’ untranslated region (3’UTR) of myotonic dystrophy protein kinase (DMPK) gene causes DM1 disease, which leads to the production of a longer, abnormal and toxic mRNA. The toxic DMPK mRNA sequester the splicing proteins such as Muscle blind-like (MBNL) and rbFOX which leads to gene expression alteration. Repeat associated non-AUG (RAN) translation also occurs in DM1. Mitochondrial dysregulation has also been reported in DM disease. So, we hypothesized that DM1 patient cells would be sensitive to environmental agents that promote increased reactive oxygen species (ROS) levels and poison the mitochondria. We have used viability assays and the mitochondrial toxicant NaAsO2 to analyze whether patient-derived cells are sensitive to this stressor. While patient-derived fibroblasts do not show clear sensitivity trends, DM1 patient-derived myotubes are sensitive to NaAsO2. We have also analyzed the codon usage of transcripts regulated in DM1 cell samples (fibroblasts, myotubes, and tibialis anterior) and identified distinct codon trends predictive of changes in RNA modification. Our work is significant because we explore new biology and exposure responses specific to Myotonic Dystrophy, specifically DM type1, and we provide seed data suggesting that patients should avoid NaAsO2 and similar environmental toxicants.