Absence of alpha 7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy

Guo, Chun, Willem, Michael, Werner, Alexander, Raivich, Gennadij, Emerson, Michael, Neyses, Ludwig and Mayer, Ulrike ORCID: https://orcid.org/0000-0003-2328-0052 (2006) Absence of alpha 7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy. Human Molecular Genetics, 15 (6). pp. 989-998. ISSN 0964-6906

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Abstract

Both the dystrophin–glycoprotein complex and α7β1 integrin have critical roles in the maintenance of muscle integrity via the provision of mechanical links between muscle fibres and the basement membrane. Absence of either dystrophin or α7 integrin results in a muscular dystrophy. To clarify the role of α7 integrin and dystrophin in muscle development and function, we generated integrin α7/dystrophin double-mutant knockout (DKO) mice. Surprisingly, DKO mice survived post-natally and were indistinguishable from wild-type, integrin α7-deficient and mdx mice at birth, but died within 24–28 days. Histological analysis revealed a severe muscular dystrophy in DKO mice with endomysial fibrosis and ectopic calcification. Weight loss was correlated with the loss of muscle fibres, indicating that progressive muscle wasting in the double mutant was most likely due to inadequate muscle regeneration. The data further support that premature death of DKO mice is due to cardiac and/or respiratory failure. The integrin α7/dystrophin-deficient mouse model, therefore, resembles the pathological changes seen in Duchenne muscular dystrophy and suggests that the different clinical severity of dystrophin deficiency in human and mouse may be due to a fine-tuned difference in expression of dystrophin and integrin α7 in both species. Together, these findings indicate an essential role for integrin α7 in the maintenance of dystrophin-deficient muscles.

Item Type:	Article
Additional Information:	© The Author 2006. Published by Oxford University Press. All rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact: journals.permissions@oxfordjournals.org
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User:	EPrints Services
Date Deposited:	01 Oct 2010 13:37
Last Modified:	24 Sep 2024 09:48
URI:	https://ueaeprints.uea.ac.uk/id/eprint/1154
DOI:	10.1093/hmg/ddl018

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