Over expression of the murine myotonic dystrophy protein kinase in the mouse myogenic C2C12 cell line leads to inhibition of terminal differentiation.

ABSTRACT

Myotonic dystrophy (DM) is an autosomal dominant human disorder, caused by the abnormal expansion of a CTG trinucleotide repeat in the 3' untranslated region of a protein kinase gene (DMPK). Muscle symptoms are a common feature of the disorder and in the adult onset cases there are increased patterns of muscle fibre degeneration and regeneration. In the congenitally affected infants there is a failure of muscle maturation, with the histological presence of numerous immature fibres. However, the pathological mechanism in both forms of the disease is unclear. We report that over-expression of the murine dmpk gene, in a murine myogenic cell line, leads to markedly reduced levels of fusion to the terminally differentiated state. These findings complement recently published data using a heterologous expression/cell system and may have implications for the understanding of the disease process in this disorder.