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Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy

Nature Genetics volume 13, pages 325–335 (1996)Cite this article

Abstract

Myotonic dystrophy (DM) is an autosomal dominant disorder resulting from the expansion of a CTG repeat in the 3′ untranslated region of a putative protein kinase (DMPK). To elucidate the role of DMPK in DM pathogenesis we have developed DMPK deficient (DMPK−/−) mice. DMPK−/− mice develop a late-onset, progressive skeletal myopathy that shares some pathological features with DM. Muscles from mature mice show variation in fibre size, increased fibre degeneration and fibrosis. Adult DMPK−/− mice show ultrastructural changes in muscle and a 50% decrease in force generation compared to young mice. Our results indicate that DMPK may be necessary for the maintenance of skeletal muscle structure and function and suggest that a decrease in DMPK levels may contribute to DM pathology.

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Authors and Affiliations

  1. Center for Cancer Research, M.I.T., Cambridge, Massachusetts, 02138, USA

    Sita Reddy, Patricia Reilly, Brigid M. Davis, Khoa Tran, Helen Rayburn & David Housman

  2. Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104-6074, USA

    Daniel B. J. Smith, Mark M. Rich, John M. Leferovich & Rita J. Balice-Gordon

  3. Department of Pathology, Tufts University Schools of Medicine and Veterinary Medicine, Boston, Massachusetts, 02111, USA

    Roderick Bronson

  4. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02214, USA

    Didier Cros

  5. Institute for Genetic Medicine, Department of Neuroscience, University of Southern California, HMR 602, 2011 Zonal Avenue, Los Angeles, California, 90033, USA

    Sita Reddy

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Reddy, S., Smith, D., Rich, M. et al. Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy. Nat Genet 13, 325–335 (1996). https://doi.org/10.1038/ng0796-325

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