Nesprin 1 is critical for nuclear positioning and anchorage

Jianlin Zhang, Amanda Felder, Yujie Liu, Ling T. Guo, Stephan Lange, Nancy D. Dalton, Yusu Gu, Kirk L. Peterson, Andrew P. Mizisin, G. Diane Shelton, Richard L. Lieber, Ju Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Nesprin 1 is an outer nuclear membrane protein that is thought to link the nucleus to the actin cytoskeleton. Recent data suggest that mutations in Nesprin 1 may also be involved in the pathogenesis of Emery-Dreifuss muscular dystrophy. To investigate the function of Nesprin 1 in vivo, we generated a mouse model in which all isoforms of Nesprin 1 containing the C-terminal spectrin-repeat region with or without KASH domain were ablated. Nesprin 1 knockout mice are marked by decreased survival rates, growth retardation and increased variability in body weight. Additionally, nuclear positioning and anchorage are dysfunctional in skeletal muscle from knockout mice. Physiological testing demonstrated no significant reduction in stress production in Nesprin 1-deficient skeletal muscle in either neonatal or adult mice, but a significantly lower exercise capacity in knockout mice. Nuclear deformation testing revealed ineffective strain transmission to nuclei in muscle fibers lacking Nesprin 1. Overall, our data show that Nesprin 1 is essential for normal positioning and anchorage of nuclei in skeletal muscle.

Original languageEnglish (US)
Article numberddp499
Pages (from-to)329-341
Number of pages13
JournalHuman molecular genetics
Volume19
Issue number2
DOIs
StatePublished - Nov 9 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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