title: Porcine models of muscular dystrophy.
abstract: 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.
authors.affiliation: Joshua T. Selsby, PhD, and Jason W. Ross, PhD are associate professors of Animal Science at Iowa State University, Ames, IA 50011. Dan Nonneman, PhD, is a research molecular biologist at the USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933. Katrin Hollinger, PhD, was a graduate student in Genetics at Iowa State University, Ames, IA 50011.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Selsby
authors.affiliation: Joshua T. Selsby, PhD, and Jason W. Ross, PhD are associate professors of Animal Science at Iowa State University, Ames, IA 50011. Dan Nonneman, PhD, is a research molecular biologist at the USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933. Katrin Hollinger, PhD, was a graduate student in Genetics at Iowa State University, Ames, IA 50011.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Ross
authors.affiliation: Joshua T. Selsby, PhD, and Jason W. Ross, PhD are associate professors of Animal Science at Iowa State University, Ames, IA 50011. Dan Nonneman, PhD, is a research molecular biologist at the USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933. Katrin Hollinger, PhD, was a graduate student in Genetics at Iowa State University, Ames, IA 50011.
authors.forename: Dan
authors.initials: D
authors.lastname: Nonneman
authors.affiliation: Joshua T. Selsby, PhD, and Jason W. Ross, PhD are associate professors of Animal Science at Iowa State University, Ames, IA 50011. Dan Nonneman, PhD, is a research molecular biologist at the USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933. Katrin Hollinger, PhD, was a graduate student in Genetics at Iowa State University, Ames, IA 50011.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hollinger
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D016189:Dystrophin / Q000378:metabolism; D051379:Mice; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D013552:Swine; D013553:Swine Diseases / Q000378:metabolism / Q000473:pathology
chemical_list: D016189:Dystrophin
keywords: Becker muscular dystrophy; DMD; Duchenne muscular dystrophy; disease model; dystrophin; mdx; pig