Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber weakness

Yotam Levy, Jacob A. Ross, Marili Niglas, Vladimir A. Snetkov, Steven Lynham, Chen Yu Liao, Megan J. Puckelwartz, Yueh Mei Hsu, Elizabeth M. McNally, Manfred Alsheimer, Stephen Dr Harridge, Stephen G. Young, Loren G. Fong, Yaiza Español, Carlos Lopez-Otin, Brian K. Kennedy, Dawn A. Lowe, Julien Ochala

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Physiological and premature aging are frequently associated with an accumulation of prelamin A, a precursor of lamin A, in the nuclear envelope of various cell types. Here, we aimed to underpin the hitherto unknown mechanisms by which prelamin A alters myonuclear organization and muscle fiber function. By experimentally studying membrane-permeabilized myofibers from various transgenic mouse lines, our results indicate that, in the presence of prelamin A, the abundance of nuclei and myosin content is markedly reduced within muscle fibers. This leads to a concept by which the remaining myonuclei are very distant from each other and are pushed to function beyond their maximum cytoplasmic capacity, ultimately inducing muscle fiber weakness.

Original languageEnglish (US)
JournalJCI Insight
Issue number19
StatePublished - Oct 4 2018


  • Aging
  • Genetic diseases
  • Muscle Biology
  • Neuromuscular disease


Dive into the research topics of 'Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber weakness'. Together they form a unique fingerprint.

Cite this