Human Molecular Genetics Advance Access originally published online on February 13, 2006
Human Molecular Genetics 2006 15(6):989-998; doi:10.1093/hmg/ddl018
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Absence of 
7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK, 2Department for Alzheimer's Research, Adolf-Butenandt-Institute, Ludwig-Maximilians-University Munich, 80336 Munich, Germany, 3Department of Neuromorphology, Max-Planck Institute for Neurobiology, 82152 Martinsried, Germany, 4Division of Cardiology, University of Manchester, Manchester M13 9PT, UK, 5Division of Biomedical Sciences, Imperial College London, London SW7 2AZ, UK and 6School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK
* To whom correspondence should be addressed. Tel: +44 1603592980; Fax:+44 1603592250; Email: u.mayer{at}uea.ac.uk
Received September 12, 2005; Accepted February 2, 2006
Both the dystrophin–glycoprotein complex and 
7ß1 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 7 integrin results in a muscular dystrophy. To clarify the role of 7 integrin and dystrophin in muscle development and function, we generated integrin 7/dystrophin double-mutant knockout (DKO) mice. Surprisingly, DKO mice survived post-natally and were indistinguishable from wild-type, integrin 7-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 7/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 7 in both species. Together, these findings indicate an essential role for integrin 7 in the maintenance of dystrophin-deficient muscles.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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