Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal
protein dystrophin. This disease has been studied using a variety of animal models including fish, mice, rats, and dogs. While these models have contributed substantially to our mechanistic understanding of the disease and
disease progression, limitations inherent to each model have slowed the clinical advancement of
therapies, which necessitates the development of novel large-animal models. Several porcine
dystrophin-deficient models have been identified, although disease severity may be so severe as to limit their potential contributions to the field. We have recently identified and completed the initial characterization of a natural porcine model of
dystrophin insufficiency. Muscles from these animals display characteristic focal
necrosis concomitant with decreased abundance and localization of
dystrophin-
glycoprotein complex components. These pigs recapitulate many of the cardinal features of
muscular dystrophy, have elevated serum
creatine kinase activity, and preliminarily appear to display altered locomotion. They also suffer from
sudden death preceded by EKG abnormalities. Pig dystrophinopathy models could allow refinement of dosing strategies in human-sized animals in preparation for clinical trials. From an animal handling perspective, these pigs can generally be treated normally, with the understanding that acute stress can lead to
sudden death. In summary, the ability to create genetically modified pig models and the serendipitous discovery of
genetic disease in the swine industry has resulted in the emergence of new animal tools to facilitate the critical objective of improving the quality and length of life for boys afflicted with such a devastating disease.