MYOTONIC-DYSTROPHY - DECREASED LEVELS OF MYOTONIN PROTEIN-KINASE (MT-PK) LEADS TO APOPTOSIS IN MUSCLE-CELLS

The pathogenesis of myotonic dystrophy (DM) and the function of the pr oduct of the DM gene, myotonin protein kinase (Mt-PK), and its relatio nship to the disease are uncertain. To gain insight into the function of Mt-PK we studied the effect of decreasing the levels of Mt-PK in cu ltured human myoblasts. Myoblasts were transfected with an anti-sense oligonucleotide (ODN) targeted to the translation initiation site of D M mRNA which resulted in about 76% reduction in the levels of Mt-PK pr otein. A large percentage (about 48 to 90%) of myoblasts transfected w ith this oligonucleotide (but only about 2 to 23% of myoblasts transfe cted with a control oligonucleotide) underwent apoptosis within 24 h. To further substantiate these results we delivered a specific antibody to Mt-PK into the myoblast cells using a lipid carrier to inhibit its function and show that this resulted in apoptosis in 57 to 72% of the cells within 24 h. These results suggest that decreased levels of Mt- PK may contribute to muscle pathology in DM by leading to apoptosis of muscle cells. (C) 1997 Academic Press.