Mutant lamins cause abnormal nuclear shape in muscle. Drosophila larval body wall muscles (magenta) expressing mutant lamins (green) have abnormally shaped nuclei. (Blue indiciates genomic DNA.) In humans, the same mutant lamin causes a rare type of muscular dystrophy.

Rare types of muscular dystrophy:

Mutations in the human LMNA gene cause a collection of diseases called laminopathies, such as muscular dystrophies, heart disease, adipose tissues disorders, and early onset aging syndromes. The LMNA gene encodes lamins, intermediate filaments that form a meshwork lining the inner nuclear membrane. Lamins provide structural support for the nucleus and play roles in genome organization, gene expression, and DNA repair. The mechanisms by which mutant lamins cause laminopathies are not well understood and there are currently no therapies. Members of the Wallrath laboratory are investigating the molecular basis of muscular dystrophies and have developed Drosophila (fruit fly) models, which provide ease of genetic and cytological analyses. Human muscle biopsy tissue is used to demonstrate disease relevance of the findings. Their studies have identified signaling pathways altered by mutant lamins and compounds that improve muscle function, providing potential new avenues for therapies.