Duchenne muscular dystrophy (DMD) is characterised by muscle degeneration that impedes mobility and severely reduces life expectancy to 20-40 years due to cardiac and/or respiratory complications. It is caused by mutations in the X-linked gene DMD that encodes dystrophin, leading to deficiency of this cohesive protein, profoundly affecting skeletal muscle. Many animal models have been developed with mutations in this gene and its homologues to enable the investigation of DMD and the development of treatments for this debilitating disease. Mouse and dog models of DMD have been the most widely used, with rat, rabbit and rhesus monkey models also having been explored. However, each of these models have limitations varying from difficulty in generating large numbers of animals or failure to recapitulate certain aspects of the human disease. Two previous studies described porcine models of DMD that recapitulate the disease, but due to side effects from gene editing procedures birth weights were variable and life expectancy was merely a few weeks.
Eckhard Wolf and colleagues have overcome these limitations in a novel porcine model of DMD developed via breeding techniques. The authors generated a female heterozygous DMD mutant sow with the deletion of exon 52, which is one of the most commonly described mutation in DMD patients. This DMD+/- carrier pig enabled scaled up breeding of DMDY/- male pigs and more female DMD+/- carrier pigs. The DMDY/- pigs mirrored many characteristic features of human DMD, including age-related alterations in tissue architecture and proteome profiles of skeletal muscle and myocardium. As well as impaired cardiac function, these pigs also displayed impaired cognitive ability, which is an often-debilitating symptom of DMD in patients. Interestingly, cardiac alterations were also present in DMD+/- carrier pigs, which mirrors observations in human carriers of mutated DMD.
DMD significantly affects morbidity and life expectancy in patients, therefore, novel treatments and techniques to accurately monitor disease progression are urgently required. Due to its striking recapitulation of human disease and scalability, this new porcine model of DMD can potentiate large-scale, longitudinal studies to investigate novel therapies and disease monitoring approaches.