Progress Update: Exploring mechanisms of myopathology in FSHD

Update by Dr. Michael Kyba

These studies have focused on understanding the pathological mechanism of FSHD, i.e. how DUX4 expression ultimately leads to loss of skeletal muscle and its replacement with fat and scar tissue. Using our recently developed FSHD mouse model, named the iDUX4pA mouse, we have provoked muscle disease by causing skeletal muscle fibers of this mouse to express the DUX4 gene at extremely low levels for a period of 6 months. We have focused specifically on the behavior of fibroblasts, the cells responsible for secreting extracellular matrix. This fibrous material, which normally surrounds and separates cells, becomes greatly overproduced under these conditions, leading to fibrosis and scar deposition within muscle. Our studies have identified altered molecular pathways operating within the fibroblast cells, which we hypothesize are responsible for muscle fibrosis in this animal model, as well as in FSHD in humans. These studies give insight into the pathological processes that lead to muscle loss in FSHD.

See grant Exploring mechanisms of myopathology in FSHD