Absence of integrin alpha 7 causes a novel form of muscular dystrophy

Mayer, U, Saher, G, Fässler, R, Bornemann, A, Echtermeyer, F, von der Mark, H, Miosge, N, Pöschl, E and von der Mark, K (1997) Absence of integrin alpha 7 causes a novel form of muscular dystrophy. Nature Genetics, 17 (3). pp. 318-23. ISSN 1061-4036

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Abstract

Integrin alpha 7 beta 1 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 alpha 7 subunit is expressed mainly in skeletal and cardiac muscle and has been suggested to be involved in differentiation and migration processes during myogenesis. Three cytoplasmic and two extracellular splice variants that have been described are developmentally regulated and expressed in different sites in the muscle. In adult muscle, the alpha 7A and alpha 7B subunits are concentrated in myotendinous junctions but can also be detected in neuromuscular junctions and along the sarcolemmal membrane. To study the potential involvement of alpha 7 integrin, during myogenesis and its role in muscle integrity and function, we generated a null allele of the alpha 7 gene (Itga7) 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 alpha 7 beta 1 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 alpha 7 beta 1 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.

Item Type: Article
Uncontrolled Keywords: animals,antigens, cd,extremities,female,flow cytometry,homozygote,integrin alpha chains,male,mice,mice, inbred strains,mice, inbred mdx,mice, transgenic,molecular sequence data,muscle fibers, skeletal,muscle, skeletal,muscular dystrophy, animal,phagocytosis,recombination, genetic,tenascin,tendons
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Pure Connector
Date Deposited: 13 Jan 2016 12:01
Last Modified: 11 Apr 2019 14:53
URI: https://ueaeprints.uea.ac.uk/id/eprint/56286
DOI: 10.1038/ng1197-318

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