Exon-skipping rat model of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by pathogenic variants in the DMD gene, which encodes dystrophin, a protein essential for maintaining muscle fiber integrity. Loss of dystrophin results in progressive skeletal muscle degeneration, cardiomyopathy and shorter lifespan. Some variants lead to Becker muscular dystrophy (BMD), a milder phenotype marked by partially functional dystrophin. Because disease severity strongly depends on mutation type and location, clinically relevant animal models are essential for developing mutation-specific therapies. However, existing models have limitations. The widely used mdx mouse shows a relatively mild phenotype, and although the recently developed DMD rat models better recapitulate human disease, no model has specifically addressed deletions in exon 45, the most frequent single-exon deletion observed in patients with DMD.