Article (Scientific journals)
Absence of alpha 7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy.
Guo, Chun; Willem, Michael; Werner, Alexander et al.
2006In Human molecular genetics, 15 (6), p. 989-98
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Keywords :
Animals; Antigens, CD/genetics; Disease Models, Animal; Dystrophin/deficiency/genetics; Female; Humans; Integrin alpha Chains/deficiency/genetics; Laminin/biosynthesis/genetics; Male; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Mice, Knockout; Muscle, Skeletal/metabolism/pathology; Muscular Dystrophy, Duchenne/genetics/metabolism/mortality/pathology; Myocardium/pathology; Regeneration/genetics; Respiratory System/pathology; Species Specificity
Abstract :
[en] Both the dystrophin-glycoprotein complex and alpha7beta1 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 alpha7 integrin results in a muscular dystrophy. To clarify the role of alpha7 integrin and dystrophin in muscle development and function, we generated integrin alpha7/dystrophin double-mutant knockout (DKO) mice. Surprisingly, DKO mice survived post-natally and were indistinguishable from wild-type, integrin alpha7-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 alpha7/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 alpha7 in both species. Together, these findings indicate an essential role for integrin alpha7 in the maintenance of dystrophin-deficient muscles.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Guo, Chun
Willem, Michael
Werner, Alexander
Raivich, Gennadij
Emerson, Michael
Neyses, Ludwig ;  University of Luxembourg > Research Office
Mayer, Ulrike
Language :
English
Title :
Absence of alpha 7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy.
Publication date :
2006
Journal title :
Human molecular genetics
ISSN :
0964-6906
Volume :
15
Issue :
6
Pages :
989-98
Peer reviewed :
Peer reviewed
Available on ORBilu :
since 16 October 2014

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