Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies.

Authors: Chen, CY  Chi, YH  Mutalif, RA  Starost, MF  Myers, TG  Anderson, SA  Stewart, CL  Jeang, KT 
Citation: Chen CY, etal., Cell. 2012 Apr 27;149(3):565-77. doi: 10.1016/j.cell.2012.01.059.
Pubmed: (View Article at PubMed) PMID:22541428
DOI: Full-text: DOI:10.1016/j.cell.2012.01.059

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 LmnaDelta9 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 LmnaDelta9 fibroblasts have typically misshapen nuclei. Unexpectedly, Lmna(-/-) or LmnaDelta9 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(-/-), LmnaDelta9, and HGPS disorders.


Disease Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 10044242
Created: 2015-06-04
Species: All species
Last Modified: 2015-06-04
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.