SCI faculty member explores the pathological mechanisms of chronic muscle disease

Muscular dystrophies are chronic degenerative diseases that can progress slowly over decades, and hence it can be difficult to decipher the pathological mechanisms at play. Dr. Michael Kyba's group has developed a mouse model of one such disease, fasioscapulohumeral muscular dystrophy (FSHD), which is caused by the loss of repression of the DUX4 gene, leading to low levels of the DUX4 protein in affected individuals' muscles. How these small amounts of the DUX4 protein cause muscle degeneration is very difficult to study in humans.

The Kyba group has stimulated long-term DUX4 expression in small numbers of muscle cells of mice to simulate the disease as it presents in humans. They discovered that this produced a muscle pathology and changes in muscle gene expression that is similar to that seen in humans with FSHD. This model provides new insight into the disease progression and the mechanism of muscle pathology, including the role of infiltrating cells in muscle pathogenesis, opening up new avenues to explore in the pursuit of treatments for this debilitating disease. Read more.