DYSTROPHIN ABNORMALITIES IN DUCHENNE AND BECKER DYSTROPHY CARRIERS - CORRELATION WITH CYTOSKELETAL PROTEINS AND MYOSINS

Characterization with a panel of six antibodies revealed abnormal dyst rophin expression in 6 of 20 Duchenne muscular dystrophy (DMD) carrier s examined, and in 5 of 12 Becker muscular dystrophy (BMD) carriers ex amined. The immunocytochemistry of muscle fibres was normal with five of the antibodies in two BMD carriers, but some muscle fibres were neg ative to the antibody directed against a portion of the dystrophin rod domain. Mosaicism was detected with all six antibodies in the other t hree BMD (but in only a small number of fibres) and in all DMD carrier muscles. Spectrin, vinculin and talin were immunolocalized in the sam e muscle specimens in order to assess membrane cytoskeletal integrity and to correlate their expression with that of dystrophin. These prote ins, including vinculin, which was previously reported to be reduced i n DMD patient muscles, were normally present on the surface of all dys trophin-deficient fibres. Muscle fibre types were characterized using monoclonal antibodies against fetal myosin and adult fast and adult sl ow myosin heavy chains. In both the DMD and BMD carriers, a significan t reduction in type 2B fibres, as well as an increase in type 2C and f etal myosin-containing fibres was found - as has also been reported in DMD patients. Altered dystrophin expression was observed more frequen tly in type 2 than type 1 fibres. Dystrophin deficiency was found in a high percentage of type 2C fibres as well as in all fibres expressing fetal myosin; this suggests that dystrophin-deficient fibres are more susceptible to degeneration, leading to regeneration.