2014
DOI: 10.1371/journal.pgen.1004114
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Targeted Ablation of Nesprin 1 and Nesprin 2 from Murine Myocardium Results in Cardiomyopathy, Altered Nuclear Morphology and Inhibition of the Biomechanical Gene Response

Abstract: Recent interest has focused on the importance of the nucleus and associated nucleoskeleton in regulating changes in cardiac gene expression in response to biomechanical load. Mutations in genes encoding proteins of the inner nuclear membrane and nucleoskeleton, which cause cardiomyopathy, also disrupt expression of a biomechanically responsive gene program. Furthermore, mutations in the outer nuclear membrane protein Nesprin 1 and 2 have been implicated in cardiomyopathy. Here, we identify for the first time a… Show more

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Cited by 131 publications
(132 citation statements)
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“…This report is consistent with the finding that depletion of the nucleoplasmic alpha isoform of LAP2 causes cardiac dysfunction in mice [48]. Mutations and polymorphisms in SYNE1 and SYNE2 genes, which respectively encode the KASH domain proteins nesprin-1 and nesprin-2, have also been reported in patients with muscular dystrophy and cardiomyopathy; disruption of the orthologous genes in mice causes skeletal and cardiac myopathy [49][50][51][52]. A mutation in SYNE1 has also been linked to an autosomal recessive form of arthrogryposis multiplex congenita, a syndrome of congenital joint contractures that results from reduced fetal movement [53].…”
Section: Muscular Dystrophysupporting
confidence: 89%
“…This report is consistent with the finding that depletion of the nucleoplasmic alpha isoform of LAP2 causes cardiac dysfunction in mice [48]. Mutations and polymorphisms in SYNE1 and SYNE2 genes, which respectively encode the KASH domain proteins nesprin-1 and nesprin-2, have also been reported in patients with muscular dystrophy and cardiomyopathy; disruption of the orthologous genes in mice causes skeletal and cardiac myopathy [49][50][51][52]. A mutation in SYNE1 has also been linked to an autosomal recessive form of arthrogryposis multiplex congenita, a syndrome of congenital joint contractures that results from reduced fetal movement [53].…”
Section: Muscular Dystrophysupporting
confidence: 89%
“…Many of these responses appear quite ubiquitous and can be observed in a number of different cell lines, including fibroblasts, myotubes, and neonatal cardiac myocytes (Banerjee et al, 2014; Ho et al, 2013b; Lammerding et al, 2004). Intriguingly, cells lacking the nuclear envelope proteins lamin A/C (Lammerding et al, 2004), emerin (Lammerding et al, 2005b), or nesprins-1 and -2 (Banerjee et al, 2014) have significantly attenuated expression of Egr-1 and Iex-1 when subjected to cyclic strain, despite normal or even increased activation of cytoplasmic MAPK signaling. These findings provided the first experimental clues depicting the role of the nucleus in cellular mechanotransduction.…”
Section: The Case For Nuclear Mechanotransduction – Getting To Thementioning
confidence: 99%
“…These mice had an increased epidermal thickness, and wound healing experiments showed a delayed closure of the wound underlining its importance in this organ[23]. Targeting of the Syne2 region near the C-terminus in combination with loss of Syne1 C-terminal isoforms in a cardiomyocyte specific fashion led to early onset cardiomyopathy[24]. Investigation of the role of KASH-domain containing Nesprin-1 and Nesprin-2 isoforms in positioning of nuclei in muscle fibers revealed an impact of Nesprin-1 but not of Nesprin-2.…”
Section: Introductionmentioning
confidence: 99%