| First Author | Lammerding J | Year | 2004 |
| Journal | J Clin Invest | Volume | 113 |
| Issue | 3 | Pages | 370-8 |
| PubMed ID | 14755334 | Mgi Jnum | J:87563 |
| Mgi Id | MGI:3027179 | Doi | 10.1172/JCI19670 |
| Citation | Lammerding J, et al. (2004) Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J Clin Invest 113(3):370-8 |
| abstractText | 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. |
