LOCALIZATION OF MYOTONIC-DYSTROPHY PROTEIN-KINASE IN SKELETAL-MUSCLE AND ITS ALTERATION WITH DISEASE

Myotonic dystrophy (DM) is an autosomal dominant disorder which affect s skeletal muscle, heart, eye lens, brain, and endocrine functions. Th e disease-causing mutations are expansions of the triplet repeat CTG i n the 3' untranslated region of a locus which encodes a serine/threoni ne protein kinase that represents a new family of protein kinases. A m onoclonal antibody to a recombinant DM protein kinase (mAb DM-1) react s specifically with the 64 kDa isoform of DM protein kinase in type I fibers in skeletal muscle, the fiber type which characteristically atr ophies in the disease. Within type I fibers of normal muscle the isofo rm may be localized with mAb DM-I to the triad region. In the DM disea se state, the enzyme is redistributed to the pathologically characteri stic peripheral sarcoplasmic masses. In markedly affected human distal myotonic muscle, the levels of the 64 kDa DM kinase isoform are eleva ted relative to slow skeletal myosin heavy chain. These results sugges t that, consistent with the dominant clinical phenotype, the localizat ion and accumulation of the 64 kDa isoform are altered in the heterozy gous disease state. (C) 1996 Wiley-Liss, Inc.