CATEGORIZING THE GENOTYPIC EXPRESSION OF DMD RELATED GENES IN BURROWING DYSTROPHIC C. ELEGANS
Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease that is characterized by muscular degeneration and weakness. DMD is an x-linked recessive genetic disorder that affects 1 in 3,500 males and is caused by the absence of the dystrophin protein. Dystrophin connects actin cytoskeleton to the extracellular matrix, which stabilizes the sarcolemma during muscle contraction. The absence of dystrophin may lead to muscle shearing and increased calcium levels in the sarcoplasmic reticulum. Consequently, the lack of dystrophin in DMD patients lead to progressive muscle deterioration and loss of mobility. The nematode Caenorhabditis elegans possess the ortholog of the dystrophin gene (dys-1) in humans. Previous DMD research on C. elegans shows that dys-1 mutant worms have moderate muscle and mobility decrease. This modest decline was most likely due to the choice of studying crawling behavior. To determine how exercise affects muscle cells in dystrophic worms, we developed a burrowing assay that allows us to see the extent of muscle degeneration and loss of mobility in these animals. Our results suggest dystrophic worms have loss in muscle fiber organization, muscle degeneration, mitochondrial blebbing, and increased levels of sarcoplasmic calcium. While the burrowing assay has finally allowed us to successfully study an animal model that portrays phenotypic characteristics of DMD, there is still so much more to discover. To study how gene expression changes in dystrophic worms affect phenotypic degeneration, we are currently assessing DMD related genes, particularly those associated with contractile muscles, mitochondrial stress, and calcium handling. We predict that due to the absence of dystrophin, these DMD related genes will be upregulated or downregulated as a means to counteract muscle degeneration. To assess differences in gene expression between healthy and dystrophic worms, we will use quantitative real time PCR (qPCR) to examine changes in gene expression over time. Our preliminary data shows that calmodulin is upregulated in dystrophic day one non- burrowing worms. This data is supported by previous studies that suggest dystrophic worms have higher levels of sarcoplasmic calcium. This project will help us have a better idea with what goes on at the gene level and will give us an idea of which genes to target to help restore muscle function.
Tamrazi, Monica, "CATEGORIZING THE GENOTYPIC EXPRESSION OF DMD RELATED GENES IN BURROWING DYSTROPHIC C. ELEGANS" (2019). University Research Symposium. 346.