The predicted structure of dystrophin, the protein known to be altered in Becker and Duchenne muscular dystrophy, indicates that dystrophin interacts with other proteins in muscle cells. The objectives of this grant are to determine what proteins interact with dystrophin, how and why they bind to dystrophin, and the identity of these dystrophin associated of dystrophin in normal muscle cells. The nature of the associated binding proteins and the resulting dystrophin-associated protein complex is key to understanding the importance of the dystrophin complex to muscle. This work has enormous consequences as to how the Duchenne and Becker phenotypes arise at the molecular and clinical levels. Other dystrophies such as limb-girdle (LGD) and fascioscapulahumeral (FSH) resemble the Becker phenotype. As such, it is possible that some portion of the dystrophin complex is altered in these other dystrophies. Therefore, the study of dystrophin binding proteins may uncover the defect in other, related dystrophies. In general terms, this work is of fundamental value in many areas of basic and clinical neurobiology.
|McAndrew, P E; Frostholm, A; White, R A et al. (1998) Identification and characterization of RPTP rho, a novel RPTP mu/kappa-like receptor protein tyrosine phosphatase whose expression is restricted to the central nervous system. Brain Res Mol Brain Res 56:9-21|
|Winnard, A V; Mendell, J R; Prior, T W et al. (1995) Frameshift deletions of exons 3-7 and revertant fibers in Duchenne muscular dystrophy: mechanisms of dystrophin production. Am J Hum Genet 56:158-66|
|Matsumura, K; Burghes, A H; Mora, M et al. (1994) Immunohistochemical analysis of dystrophin-associated proteins in Becker/Duchenne muscular dystrophy with huge in-frame deletions in the NH2-terminal and rod domains of dystrophin. J Clin Invest 93:99-105|
|Winnard, A V; Klein, C J; Coovert, D D et al. (1993) Characterization of translational frame exception patients in Duchenne/Becker muscular dystrophy. Hum Mol Genet 2:737-44|
|Klein, C J; Coovert, D D; Bulman, D E et al. (1992) Somatic reversion/suppression in Duchenne muscular dystrophy (DMD): evidence supporting a frame-restoring mechanism in rare dystrophin-positive fibers. Am J Hum Genet 50:950-9|
|Winnard, A V; Jia-Hsu, Y; Gibbs, R A et al. (1992) Identification of a 2 base pair nonsense mutation causing a cryptic splice site in a DMD patient. Hum Mol Genet 1:645-6|
|Burrow, K L; Coovert, D D; Klein, C J et al. (1991) Dystrophin expression and somatic reversion in prednisone-treated and untreated Duchenne dystrophy. CIDD Study Group. Neurology 41:661-6|