Expression patterns of utrophin were investigated and compared to those of dystrophin and associated proteins in skeletal muscle of rat embryos from E12 to E21 by immunohistochemistry. Utrophin was readily detected from E12 on, earlier than full-length dystrophin on E14. A shorter dystrophin isoform was observed from E12 to E16. The level of utrophin reached a maximum on E16–17 and then declined while that of dystrophin increased after E17. A complementary distribution of these two molecules was observed on E18. Beta-dystroglycan appeared as early as utrophin. Sarcoglycans, appearing from E14 on, were anchored first by utrophin and then by dystrophin. These results elucidate the chronological order of expression of the dytrophin/utrophin protein complex and indicate that this protein complex is originally stabilized by utrophin. This study supports our hypothesis that utrophin might be a developmental precursor of dystrophin.
