Mecp2-null mice provide new neuronal targets for Rett syndrome

BACKGROUND: Rett syndrome (RTT) is a complex neurological disorder that is one of the most frequent causes of mental retardation in women. A great landmark in research in this field was the discovery of a relationship between the disease and the presence of mutations in the gene that codes for the m...

ver descrição completa

Detalhes bibliográficos
Autores: Urdinguio, Rocío G., Lopez Serra, Lidia, López Nieva, Pilar, Alaminos, Miguel, Díaz Uriarte, Ramón, Fernández, Agustín F., Esteller, Manel
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2008
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/175488
Acesso em linha:https://hdl.handle.net/2445/175488
Access Level:Acceso aberto
Palavra-chave:ADN
Síndrome de Rett
Ratolins (Animals de laboratori)
Expressió gènica
DNA
Rett syndrome
Mice (Laboratory animals)
Gene expression
id ES_1d01aee5f5f534947819d5300a5a145b
oai_identifier_str oai:recercat.cat:2445/175488
network_acronym_str ES
network_name_str España
repository_id_str
spelling Mecp2-null mice provide new neuronal targets for Rett syndromeUrdinguio, Rocío G.Lopez Serra, LidiaLópez Nieva, PilarAlaminos, MiguelDíaz Uriarte, RamónFernández, Agustín F.Esteller, ManelADNSíndrome de RettRatolins (Animals de laboratori)Expressió gènicaDNARett syndromeMice (Laboratory animals)Gene expressionBACKGROUND: Rett syndrome (RTT) is a complex neurological disorder that is one of the most frequent causes of mental retardation in women. A great landmark in research in this field was the discovery of a relationship between the disease and the presence of mutations in the gene that codes for the methyl-CpG binding protein 2 (MeCP2). Currently, MeCP2 is thought to act as a transcriptional repressor that couples DNA methylation and transcriptional silencing. The present study aimed to identify new target genes regulated by Mecp2 in a mouse model of RTT. METHODOLOGY/PRINCIPAL FINDINGS: We have compared the gene expression profiles of wild type (WT) and Mecp2-null (KO) mice in three regions of the brain (cortex, midbrain, and cerebellum) by using cDNA microarrays. The results obtained were confirmed by quantitative real-time PCR. Subsequent chromatin immunoprecipitation assays revealed seven direct target genes of Mecp2 bound in vivo (Fkbp5, Mobp, Plagl1, Ddc, Mllt2h, Eya2, and S100a9), and three overexpressed genes due to an indirect effect of a lack of Mecp2 (Irak1, Prodh and Dlk1). The regions bound by Mecp2 were always methylated, suggesting the involvement of the methyl-CpG binding domain of the protein in the mechanism of interaction. CONCLUSIONS: We identified new genes that are overexpressed in Mecp2-KO mice and are excellent candidate genes for involvement in various features of the neurological disease. Our results demonstrate new targets of MeCP2 and provide us with a better understanding of the underlying mechanisms of RTT.Public Library of Science (PLoS)2021202120082021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/175488Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0003669PLoS One, 2008, vol. 3, num. 11, p. e3669https://doi.org/10.1371/journal.pone.0003669cc-by (c) Urdinguio, Rocío G. et al., 2008http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1754882026-05-29T05:05:01Z
dc.title.none.fl_str_mv Mecp2-null mice provide new neuronal targets for Rett syndrome
title Mecp2-null mice provide new neuronal targets for Rett syndrome
spellingShingle Mecp2-null mice provide new neuronal targets for Rett syndrome
Urdinguio, Rocío G.
ADN
Síndrome de Rett
Ratolins (Animals de laboratori)
Expressió gènica
DNA
Rett syndrome
Mice (Laboratory animals)
Gene expression
title_short Mecp2-null mice provide new neuronal targets for Rett syndrome
title_full Mecp2-null mice provide new neuronal targets for Rett syndrome
title_fullStr Mecp2-null mice provide new neuronal targets for Rett syndrome
title_full_unstemmed Mecp2-null mice provide new neuronal targets for Rett syndrome
title_sort Mecp2-null mice provide new neuronal targets for Rett syndrome
dc.creator.none.fl_str_mv Urdinguio, Rocío G.
Lopez Serra, Lidia
López Nieva, Pilar
Alaminos, Miguel
Díaz Uriarte, Ramón
Fernández, Agustín F.
Esteller, Manel
author Urdinguio, Rocío G.
author_facet Urdinguio, Rocío G.
Lopez Serra, Lidia
López Nieva, Pilar
Alaminos, Miguel
Díaz Uriarte, Ramón
Fernández, Agustín F.
Esteller, Manel
author_role author
author2 Lopez Serra, Lidia
López Nieva, Pilar
Alaminos, Miguel
Díaz Uriarte, Ramón
Fernández, Agustín F.
Esteller, Manel
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ADN
Síndrome de Rett
Ratolins (Animals de laboratori)
Expressió gènica
DNA
Rett syndrome
Mice (Laboratory animals)
Gene expression
topic ADN
Síndrome de Rett
Ratolins (Animals de laboratori)
Expressió gènica
DNA
Rett syndrome
Mice (Laboratory animals)
Gene expression
description BACKGROUND: Rett syndrome (RTT) is a complex neurological disorder that is one of the most frequent causes of mental retardation in women. A great landmark in research in this field was the discovery of a relationship between the disease and the presence of mutations in the gene that codes for the methyl-CpG binding protein 2 (MeCP2). Currently, MeCP2 is thought to act as a transcriptional repressor that couples DNA methylation and transcriptional silencing. The present study aimed to identify new target genes regulated by Mecp2 in a mouse model of RTT. METHODOLOGY/PRINCIPAL FINDINGS: We have compared the gene expression profiles of wild type (WT) and Mecp2-null (KO) mice in three regions of the brain (cortex, midbrain, and cerebellum) by using cDNA microarrays. The results obtained were confirmed by quantitative real-time PCR. Subsequent chromatin immunoprecipitation assays revealed seven direct target genes of Mecp2 bound in vivo (Fkbp5, Mobp, Plagl1, Ddc, Mllt2h, Eya2, and S100a9), and three overexpressed genes due to an indirect effect of a lack of Mecp2 (Irak1, Prodh and Dlk1). The regions bound by Mecp2 were always methylated, suggesting the involvement of the methyl-CpG binding domain of the protein in the mechanism of interaction. CONCLUSIONS: We identified new genes that are overexpressed in Mecp2-KO mice and are excellent candidate genes for involvement in various features of the neurological disease. Our results demonstrate new targets of MeCP2 and provide us with a better understanding of the underlying mechanisms of RTT.
publishDate 2008
dc.date.none.fl_str_mv 2008
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/175488
url https://hdl.handle.net/2445/175488
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0003669
PLoS One, 2008, vol. 3, num. 11, p. e3669
https://doi.org/10.1371/journal.pone.0003669
dc.rights.none.fl_str_mv cc-by (c) Urdinguio, Rocío G. et al., 2008
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Urdinguio, Rocío G. et al., 2008
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404255279906816
score 15,811543

Registros relacionados