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Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett syndrome

Nuber, Ulrike LU ; Kriaucionis, Skirmantas; Roloff, Tim C; Guy, Jacky; Selfridge, Jim; Steinhoff, Christine; Schulz, Ralph; Lipkowitz, Bettina; Ropers, H Hilger and Holmes, Megan C, et al. (2005) In Human Molecular Genetics 14(15). p.2247-2256
Abstract
Rett syndrome (RTT) is a severe form of mental retardation, which is caused by spontaneous mutations in the X-linked gene MECP2. How the loss of MeCP2 function leads to RTT is currently unknown. Mice lacking the Mecp2 gene initially show normal postnatal development but later acquire neurological phenotypes, including heightened anxiety, that resemble RTT. The MECP2 gene encodes a methyl-CpG-binding protein that can act as a transcriptional repressor. Using cDNA microarrays, we found that Mecp2-null animals differentially express several genes that are induced during the stress response by glucocorticoids. Increased levels of mRNAs for serum glucocorticoid-inducible kinase 1 (Sgk) and FK506-binding protein 51 (Fkbp5) were observed before... (More)
Rett syndrome (RTT) is a severe form of mental retardation, which is caused by spontaneous mutations in the X-linked gene MECP2. How the loss of MeCP2 function leads to RTT is currently unknown. Mice lacking the Mecp2 gene initially show normal postnatal development but later acquire neurological phenotypes, including heightened anxiety, that resemble RTT. The MECP2 gene encodes a methyl-CpG-binding protein that can act as a transcriptional repressor. Using cDNA microarrays, we found that Mecp2-null animals differentially express several genes that are induced during the stress response by glucocorticoids. Increased levels of mRNAs for serum glucocorticoid-inducible kinase 1 (Sgk) and FK506-binding protein 51 (Fkbp5) were observed before and after onset of neurological symptoms, but plasma glucocorticoid was not significantly elevated in Mecp2-null mice. MeCP2 is bound to the Fkbp5 and Sgk genes in brain and may function as a modulator of glucocorticoid-inducible gene expression. Given the known deleterious effect of glucocorticoid exposure on brain development, our data raise the possibility that disruption of MeCP2-dependent regulation of stress-responsive genes contributes to the symptoms of RTT. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
14
issue
15
pages
2247 - 2256
publisher
Oxford University Press
external identifiers
  • pmid:16002417
  • scopus:26444516160
ISSN
0964-6906
DOI
10.1093/hmg/ddi229
language
English
LU publication?
no
id
6bb74961-6a64-41eb-8791-c624d18cd46e (old id 1134210)
date added to LUP
2008-06-18 11:49:14
date last changed
2017-06-25 03:43:22
@article{6bb74961-6a64-41eb-8791-c624d18cd46e,
  abstract     = {Rett syndrome (RTT) is a severe form of mental retardation, which is caused by spontaneous mutations in the X-linked gene MECP2. How the loss of MeCP2 function leads to RTT is currently unknown. Mice lacking the Mecp2 gene initially show normal postnatal development but later acquire neurological phenotypes, including heightened anxiety, that resemble RTT. The MECP2 gene encodes a methyl-CpG-binding protein that can act as a transcriptional repressor. Using cDNA microarrays, we found that Mecp2-null animals differentially express several genes that are induced during the stress response by glucocorticoids. Increased levels of mRNAs for serum glucocorticoid-inducible kinase 1 (Sgk) and FK506-binding protein 51 (Fkbp5) were observed before and after onset of neurological symptoms, but plasma glucocorticoid was not significantly elevated in Mecp2-null mice. MeCP2 is bound to the Fkbp5 and Sgk genes in brain and may function as a modulator of glucocorticoid-inducible gene expression. Given the known deleterious effect of glucocorticoid exposure on brain development, our data raise the possibility that disruption of MeCP2-dependent regulation of stress-responsive genes contributes to the symptoms of RTT.},
  author       = {Nuber, Ulrike and Kriaucionis, Skirmantas and Roloff, Tim C and Guy, Jacky and Selfridge, Jim and Steinhoff, Christine and Schulz, Ralph and Lipkowitz, Bettina and Ropers, H Hilger and Holmes, Megan C and Bird, Adrian},
  issn         = {0964-6906},
  language     = {eng},
  number       = {15},
  pages        = {2247--2256},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett syndrome},
  url          = {http://dx.doi.org/10.1093/hmg/ddi229},
  volume       = {14},
  year         = {2005},
}