Abstract Emery-Dreifuss Muscular Dystrophy (EDMD) is a progressive disease characterized by cardiac and skeletal muscle dysfunction. A primary cause of EDMD is loss of function of the X-chromosome gene emerin (EMD). Although emerin mutations were discovered over three decades ago, X-linked EDMD (X-EDMD) remains understudied largely due to the absence of an animal model with pathological features found in humans. Here, we show that rats lacking emerin (EMD(−/y)) develop motor issues and suddenly die, a major risk factor for patients with X-EDMD. Additionally, EMD(−/y) rats present with other hallmarks of X-EDMD. We found significant fibrosis, abnormal nuclear morphologies, functional deficits and left ventricular wall thinning in the heart of EMD(−/y) rats. Skeletal muscles of EMD(−/y) rats also exhibit altered myonuclei morphology in addition to reduced muscle fiber size. In both cardiac and skeletal muscles of EMD(−/y) rats, we identified altered expression of genes with roles in the cytoskeleton, fibrosis, and muscle contraction. Some of these genes have been previously found to be dysregulated in human muscles lacking emerin. Altogether, these findings identify EMD(−/y) rats as a preclinical model of X-EDMD that phenocopies many aspects of the disease in humans. This work also revealed genes that could potentially be used as biomarkers and targets to treat X-EDMD.
Lopes et al. (2026) studied this question.