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Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice

Nature Genetics volume 13, pages 316–324 (1996)Cite this article

Abstract

Myotonic dystrophy (DM) is commonly associated with CTG repeat expansions within the gene for DM–protein kinase (DMPK). The effect of altered expression levels of DMPK, which is ubiquitously expressed in all muscle cell lineages during development, was examined by disrupting the endogenous Dmpk gene and overexpressing a normal human DMPK transgene in mice. Nullizygous (−/−) mice showed only inconsistent and minor size changes in head and neck muscle fibres at older age, animals with the highest DMPK transgene expression showed hypertrophic cardiomyopathy and enhanced neonatal mortality. However, both models lack other frequent DM symptoms including the fibre–type dependent atrophy, myotonia, cataract and male–infertility. These results strengthen the contention that simple loss– or gain–of–expression of DMPK is not the only crucial requirement for development of the disease.

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Author notes

  1. Gert Jansen

    Present address: Department of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands

  2. Gert Jansen and Patricia J.T.A. Groenen: G.J. and P.J.T.A.G. contributed equally to this work

Authors and Affiliations

  1. Department of Cell Biology and Histology, Medical Faculty, University of Nijmegen, P.O. Box 9101, 6500 MB, Nijmegen, The Netherlands

    Gert Jansen, Patricia J.T.A. Groenen, Paul H.K. Jap, Marga Coerwinkel, Frank Oerlemans, Walther van den Broek & Bé Wieringa

  2. Medical Genetics, University Ulm -Klinikum, D-89069, Ulm, Germany

    Dietmar Bächner & Horst Hameister

  3. Faculty of Biology, University of Konstanz, P.O. Box 5560 M 641, D-78434, Konstanz, Germany

    Bärbel Gohlsch & Dirk Pette

  4. Department of Physiology, University of Leiden, P.O. Box 9604, 2300 RC, Leiden, The Netherlands

    Jaap J. Plomp & Peter C. Molenaar

  5. Dept. of Cardiology, University Hospital, Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Marcel G.J. Nederhoff & Cees J.A. van Echteld

  6. Department of Molecular Genetics, Netherlands Cancer Institute, Ples-manlaan 121, Amsterdam, The Netherlands

    Marleen Dekker & Anton Berns

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Jansen, G., Groenen, P., Bächner, D. et al. Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice. Nat Genet 13, 316–324 (1996). https://doi.org/10.1038/ng0796-316

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