Mutant Dysferlin Causes Increased Rate of Differentiation in Myotubes in Dysferlinopathy Patients

Adam Kusior

Abstract:
Our topic of study is dysferlinopathy which is a rare muscular disease that causes a slow progression of muscle weakness and atrophy. Dysferlinopathy is caused by mutations in the DYSF gene which results in a deficiency of the protein dysferlin which is crucial in the repair of muscle fibers. This disease's inheritance type is autosomal recessive which means that the offspring inherits one mutated gene from each parent. In this study, we model the disease in cultured myoblasts, a muscle stem cell model. The design of this experiment is one in which we used two different cell types to test whether or not one cell type would cause an increased rate of differentiation of myotubes. Our hypothesis is that GREG (mutant) cells will become more differentiated and produce more myotubes than the C2C12 (wild-type) cells. GREG (mutant) cells do not contain the protein dysferlin, we predict that this will cause myoblasts to differentiate at a faster rate whereas C2C12 (wild-type) cells contain dysferlin which we predict will assist in muscular stem cell function and inhibits uncontrolled differentiation. We have found that GREG cells or a coculture combination of GREG cells plus C2C12 cells produce the most differentiated cells. The mutation of the protein dysferlin causes an increased rate of differentiation which results in the production of more myotubes. Some implications of our results include the patient's stem cells differentiating into myotubes too quickly causing muscle atrophy due to no new stem cells being created to replace lost muscle.