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Absence of integrin α7 causes a novel form of muscular dystrophy

Nature Genetics volume 17, pages 318–323 (1997)Cite this article

Abstract

Integrin α7β1 is a specific cellular receptor for the basement membrane protein laminin-1 (refs 1,2), as well as for the laminin isoforms -2 and -4 (ref. 3). The α7 subunit is expressed mainly in skeletal and cardiac muscle4 and has been suggested to be involved in differentiation and migration processes during myogenesis5,6.Three cytoplasmic and two extracellular splice variants that have been described are developmentally regulated and expressed in different sites in the muscle7–9. In adult muscle, the α7A and α7B subunits are concentrated in myotendinous junctions10 but can also be detected in neuromuscular junctions and along the sarcolemmal membrane11. To study the potential involvement of α7 integrin during myogenesis and its role in muscle integrity and function, we generated a null allele of the α7 gene (ItgaT) in the germline of mice by homologous recombination in embryonic stem (ES) cells. Surprisingly, mice homozygous for the mutation are viable and fertile, indicating that the α7β1 integrin is not essential for myogenesis. However, histological analysis of skeletal muscle revealed typical symptoms of a progressive muscular dystrophy starting soon after birth, but with a distinct variability in different muscle types. The observed histopathological changes strongly indicate an impairment of function of the myotendinous junctions. These findings demonstrate that αβ1 integrin represents an indispensable linkage between the muscle fibre and the extracellular matrix that is independent of the dystrophin–dystroglycan complex–mediated interaction of the cytoskeleton with the muscle basement membrane.

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Authors and Affiliations

  1. Max-Planck-Institute for Biochemistry, D-82152, Martinsried, Germany

    Ulrike Mayer, Gesine Saher & Reinhard Fässler

  2. Institute for Brain Research, University of Tübingen, D-72076, Tübingen, Germany

    Antje Bornemann

  3. Institute for Experimental Medicine, University of Erlangen-Nürnberg, D-91054, Erlangen, Germany

    Frank Echtermeyer, Helga von der Mark, Ernst Pösch & Klaus von der Mark

  4. Institute for Histology, University of Gottingen, D-37075, Göttingen, Germany

    Nicolai Miosge

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  1. Ulrike Mayer
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Correspondence to Ulrike Mayer.

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Mayer, U., Saher, G., Fässler, R. et al. Absence of integrin α7 causes a novel form of muscular dystrophy. Nat Genet 17, 318–323 (1997). https://doi.org/10.1038/ng1197-318

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