期刊
CELL
卷 149, 期 3, 页码 565-577出版社
CELL PRESS
DOI: 10.1016/j.cell.2012.01.059
关键词
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资金
- NIAID
- IATAP, NIAID
- NHRI, Taiwan [NHRI 99A1-CSPP11-014]
- NSC, Taiwan [NSC 98-2320-B-400-009-MY3]
- Singapore Biomedical Research Council
- Agency for Science, Technology and Research (AstarSTAR)
Human LMNA gene mutations result in laminopathies that include Emery-Dreifuss muscular dystrophy (AD-EDMD) and Hutchinson-Gilford progeria, the premature aging syndrome (HGPS). The Lmna null (Lmna(-/-)) and progeroid Lmna Delta 9 mutant mice are models for AD-EDMD and HGPS, respectively. Both animals develop severe tissue pathologies with abbreviated life spans. Like HGPS cells, Lmna(-/-) and Lmna Delta 9 fibroblasts have typically misshapen nuclei. Unexpectedly, Lmna(-/-) or Lmna Delta 9 mice that are also deficient for the inner nuclear membrane protein Sun1 show markedly reduced tissue pathologies and enhanced longevity. Concordantly, reduction of SUN1 overaccumulation in LMNA mutant fibroblasts and in cells derived from HGPS patients corrected nuclear defects and cellular senescence. Collectively, these findings implicate Sun1 protein accumulation as a common pathogenic event in Lmna(-/-), Lmna Delta 9, and HGPS disorders.
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