EXPRESSION OF DELETION-CONTAINING DYSTROPHINS IN MDX MUSCLE - IMPLICATIONS FOR GENE-THERAPY AND DYSTROPHIN FUNCTION

The expression of full-length dystrophin and various dystrophin deleti on mutants was monitored in mdx mouse muscle after intramuscular injec tion of dystrophin-encoding plasmid DNAs. Recombinant dystrophin prote ins, including those lacking either the amino terminus, carboxyl termi nus, or most of the central rod domain, showed localization to the pla sma membrane. This suggests that there are multiple attachment sites f or dystrophin to the plasma membrane. Only those constructs containing the carboxyl terminus were able to stabilize dystrophin-associated pr oteins (DAP) at the membrane, consistent with other studies that sugge st that this domain is critical to DAP binding. Colocalization with DA P was not necessary for membrane localization of the various dystrophi n molecules. However, stabilization and co-localization of the DAP did seem to be a prerequisite for expression and/or stabilization of muta nt dystrophins beyond 1 wk and these same criteria seemed important fo r mitigating the histopathological consequences of dystrophin deficien cy.