Relevant aspects of golden retriever muscular dystrophy for the study of Duchenne muscular dystrophy in humans

Abstract

Golden Retriever muscular dystrophy (GRMD) is the most representative model for studying Duchenne muscular dystrophy (DMD) in humans, owing its phenotypic expression. DMD is a recessive disorder linked to the X chromosome in which the loss of dystrophin induces progressive weakness and degeneration of the skeletal and cardiac muscles, which lead to replacement by connective and adipose tissues. Onset of clinical signs occurs between 2 and 5 years of age, and many patients die from heart or respiratory failure. The main studies concerning dystrophic Golden Retrievers (DGR) sought to elucidate the pathophysiology of the disease and its clinical implications to develop therapies and alternative treatments to improve the quality of life and increase longevity of DMD patients. This review presents an overview of relevant contributions of the DGR model for elucidating DMD in humans.

Mast cells in the pathophysiology of Duchenne muscular dystrophy in Golden Retriever dogs

“…Golden Retriever muscular dystrophy (GRMD) affected dogs are one of the best-known animal models of DMD, with genotypic and phenotypic manifestations similar to the human disease (Cooper et al 1988, Collins & Morgan 2003, Moraes et al 2017. GRMD dogs are the only animals that display early widespread development of secondary lesions due to deficiencies in dystrophin at two months of age.…”

“…Although mutations in dystrophin represent the main cause of DMD, disease progression is exacerbated by secondary processes that are putative for the chronic inflammation. This includes repeated cycles of degeneration and regeneration that deplete the regenerative capacity of satellite cells, and mechanisms that induce the gradual replacement of the contractile muscle tissue by connective and fatty tissue (Collins & Morgan 2003, Deconinck & Dan 2007, Miyazato et al 2011b, Moraes et al 2017. Movement becomes progressively limited, and dogs show premature signs of fatigue (Gaiad et al 2011).…”