Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry

The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis...

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Autores: Ateca-Cabarga, Juan C., Cosa-Linan, Alejandro, Pallarés, Vicente, López-Atalaya, José P., Barco, Ángel, Canals, Santiago, Moraltal Pérez, David
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/288944
Acesso em linha:http://hdl.handle.net/10261/288944
Access Level:acceso abierto
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spelling Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetryAteca-Cabarga, Juan C.Cosa-Linan, AlejandroPallarés, VicenteLópez-Atalaya, José P.Barco, ÁngelCanals, SantiagoMoraltal Pérez, DavidThe Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (−16.31%, p < 0.05), white matter volume (−16.00%, p < 0.05) and corpus callosum (−12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp+/− and cbp+/+ littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.Supported by grants from the Spanish MINECO to S.C. (BFU 2012–39958) and MINECO and FEDER to D.M. (TEC 2012–33778) and from MINECO (SAF2011-22855) and Generalitat Valenciana (Prometeo/2012/005) to A.B. The Instituto de Neurociencias is “Centre of Excellence Severo Ochoa”.Peer reviewedSpringer NatureMinisterio de Economía y Competitividad (España)European CommissionGeneralitat ValencianaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/288944reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//BFU2012-39958info:eu-repo/grantAgreement/MICINN//SAF2011-22855Scientific Reportshttps://doi.org/10.1038/srep16256Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2889442026-05-22T06:33:51Z
dc.title.none.fl_str_mv Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry
title Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry
spellingShingle Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry
Ateca-Cabarga, Juan C.
title_short Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry
title_full Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry
title_fullStr Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry
title_full_unstemmed Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry
title_sort Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry
dc.creator.none.fl_str_mv Ateca-Cabarga, Juan C.
Cosa-Linan, Alejandro
Pallarés, Vicente
López-Atalaya, José P.
Barco, Ángel
Canals, Santiago
Moraltal Pérez, David
author Ateca-Cabarga, Juan C.
author_facet Ateca-Cabarga, Juan C.
Cosa-Linan, Alejandro
Pallarés, Vicente
López-Atalaya, José P.
Barco, Ángel
Canals, Santiago
Moraltal Pérez, David
author_role author
author2 Cosa-Linan, Alejandro
Pallarés, Vicente
López-Atalaya, José P.
Barco, Ángel
Canals, Santiago
Moraltal Pérez, David
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Generalitat Valenciana
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (−16.31%, p < 0.05), white matter volume (−16.00%, p < 0.05) and corpus callosum (−12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp+/− and cbp+/+ littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.
publishDate 2015
dc.date.none.fl_str_mv 2015
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/288944
url http://hdl.handle.net/10261/288944
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO//BFU2012-39958
info:eu-repo/grantAgreement/MICINN//SAF2011-22855
Scientific Reports
https://doi.org/10.1038/srep16256
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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