Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy.
Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs.
Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA.
Joe W
JW
McGreevy
Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA.
Chady H
CH
Hakim
Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA.
Mark A
MA
McIntosh
Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA Department of Neurology, School of Medicine, University of Missouri, Columbia, MO 65212, USA duand@missouri.edu.
Dongsheng
D
Duan
D000818:Animals; D009202:Cardiomyopathies / Q000628:therapy; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency / Q000378:metabolism; D015316:Genetic Therapy; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy*; D009474:Neurons / Q000473:pathology
D016189:Dystrophin
Animal model; Canine DMD; Duchenne muscular dystrophy; Dystrophin; Gene therapy