EXPRESSION OF THE DYSTROPHIN ISOFORM DP71 IN DIFFERENTIATING HUMAN FETAL MYOGENIC CULTURES

The dystrophin gene defective in Duchenne muscular dystrophy (DMD) is extreme in size and complexity with several promoters which direct exp ression of different isoforms in different tissues, In contrast with a dult skeletal muscle which expresses 427 kDa dystrophin, fetal muscle tissue expresses the 71 kDa ubiquitous isoform Dp71 as well as 427 kDa muscle dystrophin. To examine Dp71 expression in fetal muscle further , we have monitored its expression pattern in differentiating myogenic cultures of human fetal muscle origin, The presence of transcripts in itiated from the Dp71 promoter was demonstrated by quantitative RT-PCR , The level of transcript expressed from the Dp71 promoter did not cha nge significantly during myogenic differentiation, consistent with the housekeeping nature of the promoter. Measurements to determine the st ability of the Dp71 mRNA indicated that it has a half-life of similar to 20 h and, therefore, is somewhat more stable than the larger 14 kb muscle dystrophin mRNA (t(1/2) = 16 h), In contrast with the constant level of Dp71 transcript during myogenic differentiation, the level of Dp71 protein increased significantly, perhaps due to changes in trans lation efficiency or protein stability, These results demonstrate expr ession and posttranscriptional upregulation of Dp71 in human fetal myo genic cultures.