Linked Life Data

17311848

Source:http://linkedlifedata.com/resource/pubmed/id/17311848

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 6
pubmed:dateCreated
2007-3-8
pubmed:abstractText
The dystrophin-glycoprotein complex spans the muscle plasma membrane and provides a mechanical linkage between laminin in the extracellular matrix and actin in the intracellular cytoskeleton. Within the dystrophin-glycoprotein complex, the sarcoglycans and sarcospan constitute a subcomplex of transmembrane proteins that stabilize alpha-dystroglycan, a receptor for laminin and other components of the extracellular matrix. In order to elucidate the function of sarcospan, we generated transgenic mice that overexpress sarcospan in skeletal muscle. Sarcospan transgenic mice with moderate (tenfold) levels of sarcospan overexpression exhibit a severe phenotype that is similar to mouse models of laminin-deficient congenital muscular dystrophy (MD). Sarcospan transgenic mice display severe kyphosis and die prematurely between 6 and 10 weeks of age. Histological analysis reveals that sarcospan expression causes muscle pathology marked by increased muscle fiber degeneration and/or regeneration. Sarcospan transgenic muscle does not display sarcolemma damage, which is distinct from dystrophin- and sarcoglycan-deficient muscular dystrophies. We show that sarcospan clusters the sarcoglycans into insoluble protein aggregates and causes destabilization of alpha-dystroglycan. Evidence is provided to demonstrate abnormal extracellular matrix assembly, which represents a probable pathological mechanism for the severe and lethal dystrophic phenotype. Taken together, these data suggest that sarcospan plays an important mechanical role in stabilizing the dystrophin-glycoprotein complex.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
996-1008
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Disrupted mechanical stability of the dystrophin-glycoprotein complex causes severe muscular dystrophy in sarcospan transgenic mice.
pubmed:affiliation
Department of Physiological Science, University of California, Los Angeles, CA 90095, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural