Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to α7β1-integrin deficiency

Ania L. Gheyara, Ainara Vallejo-Illarramendi, Keling Zang, Lin Mei, Rene St-Amaud, Shoukat Dedhar, Louis F. Reichardt

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Integrin-linked kinase (Ilk) is a serine/threonine kinase and an adaptor protein that links integrins to the actin cytoskeleton and to a number of signaling pathways involved in integrin action. We hypothesized that Ilk may act as an important effector of integrins in skeletal muscle, where these receptors provide a critical link between the sarcolemma and the extracellular matrix. Using the cre/lox system, we deleted Ilk from skeletal muscles of mice. The resulting mutants developed a progressive muscular dystrophy with multiple degenerating and regenerating muscle fibers, increased central nuclei, and endomysial fibrosis. These defects were widespread but were most severe near myofascial junctions where Ilk mutants showed displacement of focal adhesion-related proteins, including vinculin, paxillin, focal adhesion kinase, dystrophin, and the α7β1D-integrin subunits. Distal ends of mutant muscle fibers appeared irregular, and there was restructuring of the actin cytoskeleton. These findings resemble those seen in humans and mice lacking the α7-integrin subunit and suggest that Ilk may act as a cytoplasmic effector of α7β1-integrin in the pathogenesis of these deficiencies.

Original languageEnglish (US)
Pages (from-to)1966-1977
Number of pages12
JournalAmerican Journal of Pathology
Volume171
Issue number6
DOIs
StatePublished - Jan 1 2007

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Muscular Dystrophies
Integrins
Skeletal Muscle
Actin Cytoskeleton
Paxillin
Vinculin
Focal Adhesion Protein-Tyrosine Kinases
Muscles
Sarcolemma
Dystrophin
Focal Adhesions
Protein-Serine-Threonine Kinases
Extracellular Matrix
integrin-linked kinase
Fibrosis
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Gheyara, A. L., Vallejo-Illarramendi, A., Zang, K., Mei, L., St-Amaud, R., Dedhar, S., & Reichardt, L. F. (2007). Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to α7β1-integrin deficiency. American Journal of Pathology, 171(6), 1966-1977. https://doi.org/10.2353/ajpath.2007.070555

Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to α7β1-integrin deficiency. / Gheyara, Ania L.; Vallejo-Illarramendi, Ainara; Zang, Keling; Mei, Lin; St-Amaud, Rene; Dedhar, Shoukat; Reichardt, Louis F.

In: American Journal of Pathology, Vol. 171, No. 6, 01.01.2007, p. 1966-1977.

Research output: Contribution to journalArticle

Gheyara, AL, Vallejo-Illarramendi, A, Zang, K, Mei, L, St-Amaud, R, Dedhar, S & Reichardt, LF 2007, 'Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to α7β1-integrin deficiency', American Journal of Pathology, vol. 171, no. 6, pp. 1966-1977. https://doi.org/10.2353/ajpath.2007.070555
Gheyara, Ania L. ; Vallejo-Illarramendi, Ainara ; Zang, Keling ; Mei, Lin ; St-Amaud, Rene ; Dedhar, Shoukat ; Reichardt, Louis F. / Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to α7β1-integrin deficiency. In: American Journal of Pathology. 2007 ; Vol. 171, No. 6. pp. 1966-1977.
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