Grant: Operating Grant

Skeletal muscles make up 40% of body weight in humans. Muscles control walking, talking, sitting, standing, eating, in addition to many of the other functions that our bodies constantly perform. Muscular dystrophy is a group of genetic diseases in which the muscle forms normally but progressively degenerates, leading to loss of muscle function, and even death. Although each known type of muscular dystrophy can be traced to causal mutations in a single associated gene, human muscular dystrophy often displays a wide range of disease severity. For example, even within the same family, one patient may be severely affected whereas a sibling with exactly the same genetic defect might experience a much milder symptom, suggesting that other insults, especially secondary mutations in other genes, influence the disease outcome. Identification of these secondary mutations has been difficult due to the lack of good genetic models. Moreover, most work on muscular dystrophy for the past twenty-five years has concentrated on muscle cells themselves, while modulation of muscle integrity by the surrounding non-muscle cells has largely been overlooked. Here, we will utilize our unique zebrafish model of muscular dystrophy to examine the genetic basis of heterogeneous phenotypes observed with this disease, and ultimately seek to uncover new cells and genes that are important for muscular dystrophy.