期刊
JOURNAL OF CELL SCIENCE
卷 119, 期 11, 页码 2185-2195出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.02952
关键词
alpha 7 integrin; dystrophin; transgenic mice; double knockout; skeletal muscle; muscular dystrophy
类别
资金
- NCRR NIH HHS [P20 RR15581-04, P20 RR018751] Funding Source: Medline
The dystrophin glycoprotein complex links laminin in the extracellular matrix to the cell cytoskeleton. Loss of dystrophin causes Duchenne muscular dystrophy, the most common human X- chromosome- linked genetic disease. The alpha 7 beta 1 integrin is a second transmembrane laminin receptor expressed in skeletal muscle. Mutations in the alpha 7 integrin gene cause congenital myopathy in humans and mice. The alpha 7 beta 1 integrin is increased in the skeletal muscle of Duchenne muscular dystrophy patients and mdx mice. This observation has led to the suggestion that dystrophin and alpha 7 beta 1 integrin have complementary functional and structural roles. To test this hypothesis, we generated mice lacking both dystrophin and alpha 7 integrin ( mdx/alpha 7(-/-)). The mdx/alpha 7(-/-) mice developed early-onset muscular dystrophy and died at 2-4 weeks of age. Muscle fibers from mdx/alpha 7(-/-) mice exhibited extensive loss of membrane integrity, increased centrally located nuclei and inflammatory cell infiltrate, greater necrosis and increased muscle degeneration compared to mdx or alpha 7-integrin null animals. In addition, loss of dystrophin and/ or alpha 7 integrin resulted in altered expression of laminin-alpha 2 chain. These results point to complementary roles for dystrophin and alpha 7 beta 1 integrin in maintaining the functional integrity of skeletal muscle.
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