title: Muscular dystrophy modeling in zebrafish.
abstract: Skeletal muscle performs an essential function in human physiology with defects in genes encoding a variety of cellular components resulting in various types of inherited muscle disorders. Muscular dystrophies (MDs) are a severe and heterogeneous type of human muscle disease, manifested by progressive muscle wasting and degeneration. The disease pathogenesis and therapeutic options for MDs have been investigated for decades using rodent models, and considerable knowledge has been accumulated on the cause and pathogenetic mechanisms of this group of human disorders. However, due to some differences between disease severity and progression, what is learned in mammalian models does not always transfer to humans, prompting the desire for additional and alternative models. More recently, zebrafish have emerged as a novel and robust animal model for the study of human muscle disease. Zebrafish MD models possess a number of distinct advantages for modeling human muscle disorders, including the availability and ease of generating mutations in homologous disease-causing genes, the ability to image living muscle tissue in an intact animal, and the suitability of zebrafish larvae for large-scale chemical screens. In this chapter, we review the current understanding of molecular and cellular mechanisms involved in MDs, the process of myogenesis in zebrafish, and the structural and functional characteristics of zebrafish larval muscles. We further discuss the insights gained from the key zebrafish MD models that have been so far generated, and we summarize the attempts that have been made to screen for small molecules inhibitors of the dystrophic phenotypes using these models. Overall, these studies demonstrate that zebrafish is a useful in vivo system for modeling aspects of human skeletal muscle disorders. Studies using these models have contributed both to the understanding of the pathogenesis of muscle wasting disorders and demonstrated their utility as highly relevant models to implement therapeutic screening regimens.
authors.affiliation: Monash University, Clayton, VIC, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: The Ohio State University, Columbus, OH, United States.
authors.forename: K J
authors.initials: KJ
authors.lastname: Hromowyk
authors.affiliation: The Ohio State University, Columbus, OH, United States.
authors.forename: S L
authors.initials: SL
authors.lastname: Amacher
authors.affiliation: Monash University, Clayton, VIC, Australia.
authors.forename: P D
authors.initials: PD
authors.lastname: Currie
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007814:Larva / Q000235:genetics / Q000502:physiology; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development
keywords: Chemical screen; Dystrophin; Human disease modeling; Myogenesis; Skeletal muscle; Zebrafish