Dystrophin and utrophin expression require sarcospan: loss of α7 integrin exacerbates a newly discovered muscle phenotype in sarcospan-null mice

Hum Mol Genet. 2012 Oct 15;21(20):4378-93. doi: 10.1093/hmg/dds271. Epub 2012 Jul 13.


Sarcospan (SSPN) is a core component of the major adhesion complexes in skeletal muscle, the dystrophin- and utrophin (Utr)-glycoprotein complexes (DGC and UGC). We performed a rigorous analysis of SSPN-null mice and discovered that loss of SSPN decreased DGC and UGC abundance, leading to impaired laminin-binding activity and susceptibility to eccentric contraction-induced injury in skeletal muscle. We show that loss of SSPN increased levels of α7β1 integrin. To genetically test whether integrin compensates for the loss of DGC and UGC function in SSPN-nulls, we generated mice lacking both SSPN and α7 integrin (DKO, double knockout). Muscle regeneration, sarcolemma integrity and fibrosis were exacerbated in DKO mice and were remarkably similar to muscle from Duchenne muscular dystrophy (DMD) patients, suggesting that secondary loss of integrin contributes significantly to pathogenesis. Expression of the DGC and UGC, laminin binding and Akt signaling were negatively impacted in DKO muscle, resulting in severely diminished specific force properties. We demonstrate that SSPN is a necessary component of dystrophin and Utr function and that SSPN modulation of integrin signaling is required for extracellular matrix attachment and muscle force development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Disease Models, Animal
  • Dystrophin / genetics*
  • Female
  • Integrin alpha Chains / genetics*
  • Integrin alpha Chains / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism*
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / metabolism
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Phenotype*
  • Sarcolemma / metabolism
  • Utrophin / genetics*


  • Antigens, CD
  • Carrier Proteins
  • Dystrophin
  • Integrin alpha Chains
  • Membrane Proteins
  • Neoplasm Proteins
  • Sspn protein, mouse
  • Utrophin
  • integrin alpha7