Nature Genetics
13, 316 - 324 (1996)
doi:10.1038/ng0796-316
Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in miceGert Jansen*, 1, 7, Patricia J.T.A. Groenen*, 1, Dietmar Bächner2, Paul H.K. Jap1, Marga Coerwinkel1, Frank Oerlemans1, Walther van den Broek1, Bärbel Gohlsch3, Dirk Pette3, Jaap J. Plomp4, Peter C. Molenaar4, Marcel G.J. Nederhoff5, Cees J.A. van Echteld5, Marleen Dekker6, Anton Berns6, Horst Hameister2
& Bé Wieringa1, 8
1Department of Cell Biology and Histology, Medical Faculty, University of Nijmegen, P.O. Box 9101, 6500 MB Nijmegen, The Netherlands
2Medical Genetics, University Ulm -Klinikum, D-89069 Ulm, Germany
3Faculty of Biology, University of Konstanz, P.O. Box 5560 M 641, D-78434 Konstanz, Germany
4Department of Physiology, University of Leiden, P.O. Box 9604, 2300 RC Leiden, The Netherlands
5Dept. of Cardiology, University Hospital, Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
6Department of Molecular Genetics, Netherlands Cancer Institute, Ples-manlaan 121, Amsterdam, The Netherlands
7G.J. current address: Department of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands
*G.J. and P.J.T.A.G. contributed equally to this work
8Correspondence should be addressed to B.W. 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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