Animal models of muscular dystrophy

Abstract

The muscular dystrophies (MDs) represent a diverse collection of inherited human disorders, which affect to varying degrees skeletal, cardiac, and sometimes smooth muscle (Emery, 2002). To date, more than 50 different genes have been implicated as causing one or more types of MD (Bansal et al., 2003). In many cases, invaluable insights into disease mechanisms, structure and function of gene products, and approaches for therapeutic interventions have benefited from the study of animal models of the different MDs (Arnett et al., 2009). The large number of genes that are associated with MD and the tremendous number of animal models that have been developed preclude a complete discussion of each in the context of this review. However, we summarize here a number of the more commonly used models together with a mixture of different types of gene and MD, which serves to give a general overview of the value of animal models of MD for research and therapeutic development.

Fig. 1

The dystrophin–glycoprotein complex (DGC) contains many proteins that, when not expressed, lead to various forms of muscular dystrophy. Shown is the organization of the DGC in skeletal muscle. Dystrophin is defective in DMD and BMD; α-, β-, γ-, and δ- sarcoglycans (Sgn) are defective in four different types of LGMD; laminin α2 is defective in one form of congenital muscular dystrophy; collagen VI in the extracellular matrix is defective in Bethlem myopathy and Ullrich congenital muscular dystrophy; while numerous other cytosolic- and membrane-associated proteins lead to other MDs. Other abbreviations include Syn, syntrophin; SPN, sarcospan; Dgn, dystroglycan; nNOS, neuronal nitric oxide synthase. Dystrophin domains listed include the N-terminal actin-binding domain (NT), various hinges (H), a WW domain (W), a cysteine-rich domain (CR), and a C-terminal domain (CT). Orange and red balls in dystrophin represent spectrin-like repeats, orange ones are acidic, while blue ones are basic and contribute to actin binding.