THE CYSTEINE-RICH AND C-TERMINAL DOMAINS OF DYSTROPHIN ARE NOT REQUIRED FOR NORMAL COSTAMERIC LOCALIZATION IN THE MOUSE

Dystrophin has a modular structure and is believed to be critical for muscle cell cytoarchitecture by linking the cytoskeleton to the extrac ellular matrix. The N-terminus binds to actin and two domains at the C -terminus, the cysteine-rich and C-terminal domains, are associated wi th the sarcolemma indirectly via the dystroglycan complex. We have gen erated a mutation in mouse embryonic stem (ES) cells which serves to d elete the cysteine-rich and C-terminal domains to address directly the ir role. We show that these two domains are not necessary for normal c ostameric organization at the sarcolemma in myotubes derived from the mutant cell line. Furthermore sarcolemmal localization is also apparen t in mouse chimaeric muscle in vivo.