(CTG)n repeats markedly inhibit differentiation of the C2C12 myoblast cell line:: implications for congenital myotonic dystrophy

Although the mutation for myotonic dystrophy has been identified as a (CTG)(n) repeat expansion located in the 3'-untranslated region of a gene located on chromosome 19, the mechanism of disease pathogenesis is not understood, The objective of this study was to assess the effect of (CTG)(n) repeats on the differentiation of myoblasts in cell culture. We report here that C2C12 myoblast cell lines permanently transfected with plasmid expressing 500 bases long CTG repeat sequences, exhibited a drastic reduction in their ability to fuse and differentiate into myotubes, The percentage of cells fused into myotubes in C2 C12 cells (53.4 +/- 4.4%) was strikingly different from those in the two CTG repeat carrying clones (1.8 +/- 0.4% and 3.3 +/- 0.7%). Control C2C12 cells permanently transfected with vector alone did not show such an effect. This finding may have important implications in understanding the pathogenesis of congenital myotonic dystrophy. (C) 1999 Elsevier Science B.V. All rights reserved.