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© The Rockefeller University Press,
0021-9525/2001//1207 $5.00
The Journal of Cell Biology, Volume 152, Number 6,
, 2001 1207-1218
Original Article |
Enhanced Expression of the 
7β1 Integrin Reduces Muscular Dystrophy and Restores Viability in Dystrophic Mice
stephenk{at}uiuc.edu
Muscle fibers attach to laminin in the basal lamina using two distinct mechanisms: the dystrophin glycoprotein complex and the
7β1 integrin. Defects in these linkage systems result in Duchenne muscular dystrophy (DMD), 2 laminin congenital muscular dystrophy, sarcoglycan-related muscular dystrophy, and 7 integrin congenital muscular dystrophy. Therefore, the molecular continuity between the extracellular matrix and cell cytoskeleton is essential for the structural and functional integrity of skeletal muscle. To test whether the 7β1 integrin can compensate for the absence of dystrophin, we expressed the rat 7 chain in mdx/utr–/– mice that lack both dystrophin and utrophin. These mice develop a severe muscular dystrophy highly akin to that in DMD, and they also die prematurely. Using the muscle creatine kinase promoter, expression of the 7BX2 integrin chain was increased 2.0–2.3-fold in mdx/utr–/– mice. Concomitant with the increase in the 7 chain, its heterodimeric partner, β1D, was also increased in the transgenic animals. Transgenic expression of the 7BX2 chain in the mdx/utr–/– mice extended their longevity by threefold, reduced kyphosis and the development of muscle disease, and maintained mobility and the structure of the neuromuscular junction. Thus, bolstering 7β1 integrin–mediated association of muscle cells with the extracellular matrix alleviates many of the symptoms of disease observed in mdx/utr–/– mice and compensates for the absence of the dystrophin- and utrophin-mediated linkage systems. This suggests that enhanced expression of the 7β1 integrin may provide a novel approach to treat DMD and other muscle diseases that arise due to defects in the dystrophin glycoprotein complex. A video that contrasts kyphosis, gait, joint contractures, and mobility in mdx/utr–/– and 7BX2-mdx/utr–/–mice can be accessed at http://www.jcb.org/cgi/content/full/152/6/1207.
Key Words: 7β1 integrin • muscular dystrophy • dystrophin • utrophin • neuromuscular junction
© 2001 The Rockefeller University Press
The online version of this article contains supplemental material.Abbreviations used in this paper: AChR, acetylcholine receptor; DMD, Duchenne muscular dystrophy; fMyHC, fetal myosin heavy chain; MCK, muscle creatine kinase, MRI, magnetic resonance imaging; NMJ, neuromuscular junction.
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