Dystonin-deficient mice exhibit an intrinsic muscle weakness and an instability of skeletal muscle cytoarchitecture

Dev Biol. 1999 Jun 15;210(2):367-80. doi: 10.1006/dbio.1999.9263.


Dystonia musculorum (dt) was originally described as a hereditary sensory neurodegeneration syndrome of the mouse. The gene defective in dt encodes a cytoskeletal linker protein, dystonin, that is essential for maintaining neuronal cytoskeletal integrity. In addition to the nervous system, dystonin is expressed in a variety of other tissues, including muscle. We now show that dystonin cross-links actin and desmin filaments and that its levels are increased during myogenesis, coinciding with the progressive reorganization of the intermediate filament network. A disorganization of cytoarchitecture in skeletal muscle from dt/dt mice was observed in ultrastructural studies. Myoblasts from dt/dt mice fused to form myotubes in culture; however, terminally differentiated myotubes contained incompletely assembled myofibrils. Another feature observed in dt/dt myotubes in culture and in skeletal muscle in situ was an accumulation and abnormal distribution of mitochondria. The diaphragm muscle from dt/dt mice was weak in isometric contractility measurements in vitro and was susceptible to contraction-induced sarcolemmal damage. Altogether, our data indicate that dystonin is a cross-linker of actin and desmin filaments in muscle and that it is essential for establishing and maintaining proper cytoarchitecture in mature muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Carrier Proteins*
  • Cell Differentiation
  • Cell Line
  • Cross-Linking Reagents
  • Cytoskeletal Proteins / deficiency*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Desmin / metabolism
  • Diaphragm / pathology
  • Diaphragm / physiopathology
  • Diaphragm / ultrastructure
  • Dystonin
  • Gene Expression Regulation, Developmental
  • Isometric Contraction
  • Mice
  • Mice, Mutant Strains
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology*
  • Muscle, Skeletal / ultrastructure
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Actins
  • Carrier Proteins
  • Cross-Linking Reagents
  • Cytoskeletal Proteins
  • Desmin
  • Dst protein, mouse
  • Dystonin
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins