Linked Life Data

15115765

Source:http://linkedlifedata.com/resource/pubmed/id/15115765

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-5-24
pubmed:abstractText
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in MECP2, encoding methyl-CpG-binding protein 2 (MeCP2). The onset of symptoms in RTT is delayed until 6-18 months and 4-6 months in the Mecp2(-/+) mouse model, corresponding to a dynamic and gradual accumulation of MeCP2 expression in individual neurons of the postnatal brain. Because of X chromosome inactivation (XCI), cells within RTT females are mosaic for expression of the heterozygous MECP2 mutation. Using the targeted Mecp2 mouse model, we investigated the effect of Mecp2 mutation on XCI and developmental MeCP2 expression in wild-type (wt)-expressing neurons by quantitative laser scanning cytometry. Mecp2(-/+) female mice exhibited uniform regional distribution of Mecp2 mutant-expressing cells in brain, but unbalanced XCI in the population, favoring expression of the Mecp2 wt allele. Interestingly, MeCP2 expression in Mecp2 wt-expressing cells from Mecp2(-/+) mice was significantly lower than those from Mecp2(+/+) age-matched controls. The negative effect of Mecp2 mutation on wt Mecp2 expression correlated with the percentage of Mecp2 mutant-expressing cells in the cortex. Similar results were observed in two RTT females with identical MECP2 mutations but different XCI ratios. These results demonstrate that Mecp2-mutant neurons affect the development of surrounding neurons in a non-cell-autonomous manner and suggest that environmental influences affect the level of MeCP2 expression in wt neurons. These results help in explaining the role of XCI in the pathogenesis of RTT and have important implications in designing therapies for female RTT patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1275-86
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
X-Chromosome inactivation ratios affect wild-type MeCP2 expression within mosaic Rett syndrome and Mecp2-/+ mouse brain.
pubmed:affiliation
Medical Microbiology and Immunology, Rowe Program in Human Genetics, School of Medicine, University of California, Davis 95616, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't