The golden retriever model of Duchenne muscular dystrophy

摘要: Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the DMD gene and loss of protein dystrophin. The absence dystrophin leads to myofiber membrane fragility necrosis, with eventual muscle atrophy contractures. Affected boys typically die their second or third decade due either respiratory failure cardiomyopathy. Despite extensive attempts develop definitive therapies for DMD, standard care remains prednisone, which has only palliative benefits. Animal models, mainly mdx mouse golden retriever (GRMD) dog, have played a key role studies pathogenesis treatment development. Because GRMD clinical syndrome more severe than mice, better aligning progressive course canine may translate humans. original founder dog all colonies worldwide was identified early 1980s before discovery Accordingly, analogies were initially drawn based on similar features, ranging from pattern inheritance overlapping histopathologic lesions. Confirmation genetic homology between came identification underlying mutation, single nucleotide change that exon skipping out-of-frame transcript. subsequently been established conduct pathogenetic preclinical studies. Simultaneous onset trials, phenotypic biomarkers developed, allowing characterization effect. Importantly, not always substantiated findings mice sometimes serious side effects. While model be clinically relevant mouse, usage limited practical considerations related expense number dogs available. This further complicates ongoing broader concerns about poor rate translation animal humans analogous diseases. performing special attention must paid experimental design align approach used trials. review provides context model, beginning its description extending use