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Figure 6


Fig. 6. (A) A region of a myotube around one nucleus (a cytoplasmic domain) that has contributed dystrophin expression to the myotube through fusion during myotube formation. Tissue culture experiments examined the dynamics of domain elongation in culture, using different proportions of co-cultured normal (dystrophin-positive) and dystrophic (dystrophin-negative) satellite cells (Kong and Anderson, 2001). (B) Micrograph showing expression of developmental myosin heavy chain (devMHC) in new myotubes formed over 4 days of regeneration following injury to normal muscle. (C) Micrograph showing laminin immunostaining surrounding skeletal muscle fibres. Laminin is one of the external matrix proteins that is complexed with the dystrophin-associated proteins that are either internal, transmembrane or linked with proteins inside the sarcolemma in normal muscle (Crawford et al., 2000; Ervasti and Campbell, 1993; Ferletta et al., 2003). In muscles affected by mutations in proteins of the dystrophin-associated protein complex, the expression of laminin is reduced; this is also noted in dystrophin-deficient muscle (Ferletta et al., 2003; Kanagawa et al., 2005; Kikkawa et al., 2004; Kim et al., 2004; Saito et al., 2005). Treatment with glucocorticoids increases the expression of laminin in mdx mouse skeletal muscle (Anderson et al., 2000). NOS-1 expression is also reduced secondary to dystrophin deficiency. There is significant alleviation of the dystrophic phenotype (in the mdx dystrophic mouse) by increasing the expression of NOS-1 in mdx mouse skeletal muscle (using transgenic approaches) and the use of a NOS substrate (L-arginine) to reduce the severity and progression of mdx mouse muscular dystrophy (Anderson, 2000; Anderson et al., 2005; Anderson and Vargas, 2003; Archer et al., 2006; Brenman et al., 1995; Brenman et al., 1996; Shiao et al., 2004; Tidball and Wehling-Henricks, 2004a; Tidball and Wehling-Henricks, 2004b; Wehling et al., 2001; Wehling-Henricks et al., 2005). (Original micrographs all x140.)





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