Accumulation of the Inner Nuclear Envelope Protein Sun1 Is Pathogenic in Progeric and Dystrophic Laminopathies
Copyright policy )Accumulation of the Inner Nuclear Envelope Protein Sun1 Is Pathogenic in Progeric and Dystrophic Laminopathies
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 LmnaΔ9 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 LmnaΔ9 fibroblasts have typically misshapen nuclei. Unexpectedly, Lmna(-/-) or LmnaΔ9 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(-/-), LmnaΔ9, and HGPS disorders.
- National Institutes of Health United States
- National Institute of Allergy and Infectious Diseases United States
- National Institute of Health Pakistan
- National University of Singapore Libraries Singapore
- National Health Research Institutes Taiwan
Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Membrane Proteins, Nuclear Proteins, Fibroblasts, Lamin Type A, Muscular Dystrophy, Emery-Dreifuss, Cell Line, Disease Models, Animal, Mice, Progeria, Animals, Humans, Microtubule-Associated Proteins, Cellular Senescence
Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Membrane Proteins, Nuclear Proteins, Fibroblasts, Lamin Type A, Muscular Dystrophy, Emery-Dreifuss, Cell Line, Disease Models, Animal, Mice, Progeria, Animals, Humans, Microtubule-Associated Proteins, Cellular Senescence
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