Project: Modeling Freeman Sheldon Syndrome in Mouse-derived Skeletal Myocytes
Freeman-Sheldon Syndrome (FSS) is a rare skeletal muscle disease that is characterized by a small mouth opening and malformation of the hands and feet. A mutation within a muscle protein, myosin, is the genetic basis of this disease but the mechanisms by which the mutation disrupts development isn’t understood. I will gene edit mouse cells with CRISPR-Cas9 technology to study this disease and the physiological process of fetal muscle development. First, I will introduce a point mutation into embryonic myosin that causes FSS, and second, I will remove the embryonic myosin gene. After studying both FSS and embryonic myosin in a cellular context, the second part of my project will involve studying protein function in vitro by infecting muscle cells with a virus containing embryonic myosin bearing the FSS mutation. By looking at both the cellular context of FSS and the contractile protein properties, this data will elucidate mechanisms of FSS disease progression, and provide a better understanding of the role of embryonic myosin during muscle development.