Asset Details
Do you wish to reserve the book?
Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome
Do you wish to request the book?
Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome
2005
Overview
Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by
LMNA
), one of the major architectural elements of the mammalian cell nucleus
1
,
2
,
3
,
4
. The HGPS mutation activates an aberrant cryptic splice site in
LMNA
pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A
3
,
4
. Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant
LMNA
mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
