Rare DYSF Protein Mutation Causes Increased Differentiation Rate in Appendicular Muscles Cells Resulting in Muscular Atrophy

Michaela Mancuso

Abstract:
The goal of our research is to characterize the onset and progression of Dysferlinopathy, a rare form of muscular dystrophy caused by recessive genetic mutation that misfolds dysferlin (DYSF), the membrane repairing protein in mammalian cells. Without DYSF the patient will experience a progressive loss of muscle mass caused by the loss of cells in appendicular muscles. Loss of the DYSF, calcium dependent, protein results in an inability to effectively repair damaged muscle cell membranes by recruiting membrane vesicles to the place of damage. We will demonstrate this repair mechanism by growing and manipulating immature muscle cells, or myoblasts, with and without the DYSF gene. We hypothesize that mutant cells lacking the DYSF gene promote increased differentiation of myoblasts into mature muscle fibers. Pre-established literature has focused on the role of dysferlin in the system's ability to repair cellular membranes. We, on the other hand, are working to prove mutation to DYSF protein causes a loss of skeletal stem cell population. By establishing populations of these two cell lines, cells with and without DYSF, we can test how Dysferlinopathy mutation impacts the maturation rate of myoblasts.