Freeman-Sheldon Syndrome (FSS) is a genetic disease where patients exhibit musculoskeletal abnormalities such as joint deformities, bent fingers, club feet, curved spine and facial anomalies. FSS patients have compromised movement, respiratory, speech and feeding problems and delayed growth and development. Mutations in the MYH3 gene, a gene belonging to the myosin family which helps in muscle contraction, has been reported to be the primary cause of FSS.Interestingly, how mutations in the MYH3 gene leads to musculoskeletal abnormalities seen in FSS patients is unclear.
In recent work from our laboratory, we have used thefruit flyDrosophila melanogaster, agenetic model, to understand the muscular abnormalities that occur in FSS patients. For this, we generated fruit flies expressing the FSS mutant myosin and characterized the abnormalities in muscle structure and function. The muscle is made up of numerous muscle fibers, which in turn contain sarcomeres, the functional contractile units of the muscle. We find that expressing the FSS mutant myosin leads to severe muscle defects such as shortening of the length and width of the sarcomeres, splitting of muscle fibers,aberrantmuscle contraction and reduced climbing capability. Interestingly, these defects became more severe with age and muscle use.
Thus, using the fruit fly, we have characterized what goes wrong in the muscle of Freeman Sheldon Syndrome patients. Using this disease model, we would now like to identify potential strategies to alleviate the muscle defects, which should provide new approachesto treating patients born with this disorder.
Das, S., Kumar, P., Verma, A., Maiti, T.K., and Mathew, S.J., 2019. Myosin heavy chain mutations that cause Freeman-Sheldon Syndrome lead to muscle structural and functional defects in Drosophila.
Full Artical: https://doi.org/10.1016/j.ydbio.2019.02.017