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Inactivation of muscle chloride channel by transposon insertion in myotonic mice

Nature volume 354, pages 304308 (28 November 1991) | Download Citation

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Abstract

MYOTONIA (stiffness and impaired relaxation of skeletal muscle) is a symptom of several diseases caused by repetitive firing of action potentials in muscle membranes1. Purely myotonic human diseases are dominant myotonia congenita (Thomsen) and recessive generalized myotonia (Becker), whereas myotonic dystrophy is a systemic disease. Muscle hyperexcitability was attributed to defects in sodium channels2,3 and/or to a decrease in chloride conductance (in Becker's myotonia4 and in genetic animal models5–10). Experimental blockage of Cl conductance (normally 70–85% of resting conductance in muscle11) in fact elicits myotonia1,9. ADR (ref. 12) mice are a realistic animal model5–7,12–18 for recessive autosomal myotonia. In addition to Cl conductance5, many other parameters6,12,16 are changed in muscles of homozygous animals. We have now cloned the major mammalian skeletal muscle chloride channel (C1C-1)19. Here wereport that in ADR mice a transposon of the ETn family20–23 has inserted into the corresponding gene, destroying its coding potential for several membrane-spanning domains. Together with the lack of recombination between the Clc-1 gene and the adr locus, this strongly suggests a lack of functional chloride channels as the primary cause of mouse myotonia.

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Affiliations

  1. Centre for Molecular Neurobiology (ZMNH), Hamburg University, Martinistrasse 52, D-2000 Hamburg 20, Germany

    • Klaus Steinmeyer
    • , Christoph Ortland
    • , Stefan GrÜnder
    •  & Thomas J. Jentsch
  2. Developmental Biology Unit, W7, Bielefeld University, PO Box 8640, D-4800 Bielefeld 1, Germany

    • Rainer Klocke
    • , Monika Gronemeier
    •  & Harald Jockusch

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https://doi.org/10.1038/354304a0

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