Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction

J Clin Invest. 2004 Feb;113(3):370-8. doi: 10.1172/JCI19670.


Mutations in the lamin A/C gene (LMNA) cause a variety of human diseases including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and Hutchinson-Gilford progeria syndrome. The tissue-specific effects of lamin mutations are unclear, in part because the function of lamin A/C is incompletely defined, but the many muscle-specific phenotypes suggest that defective lamin A/C could increase cellular mechanical sensitivity. To investigate the role of lamin A/C in mechanotransduction, we subjected lamin A/C-deficient mouse embryo fibroblasts to mechanical strain and measured nuclear mechanical properties and strain-induced signaling. We found that Lmna-/- cells have increased nuclear deformation, defective mechanotransduction, and impaired viability under mechanical strain. NF-kappaB-regulated transcription in response to mechanical or cytokine stimulation was attenuated in Lmna-/- cells despite increased transcription factor binding. Lamin A/C deficiency is thus associated with both defective nuclear mechanics and impaired mechanically activated gene transcription. These findings suggest that the tissue-specific effects of lamin A/C mutations observed in the laminopathies may arise from varying degrees of impaired nuclear mechanics and transcriptional activation.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Nucleus / metabolism*
  • Cytoskeleton / metabolism
  • Fibroblasts
  • Flow Cytometry
  • Lamin Type A / deficiency*
  • Lamin Type A / genetics
  • Lamin Type A / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Signal Transduction / physiology*


  • Lamin Type A
  • NF-kappa B