Essential role of the N-terminal region of TFII-I in viability and behavior

Background: GTF2I codes for a general intrinsic transcription factor and calcium channel regulator TFII-I, with high and ubiquitous expression, and a strong candidate for involvement in the morphological and neuro-developmental anomalies of the Williams-Beuren syndrome (WBS). WBS is a genetic disord...

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Autores: Lucena, Jaume, Pezzi, Susana, Aso, Ester, Valero, Maria C., Carreiro, Candelas, Dubus, Pierre, Sampaio, Adriana, Segura, Maria, Barthelemy, Isabel, Zindel, Marc Y., Sousa, Nuno, Barbero, Jose L., Maldonado, Rafael, Perez-Jurado, Luis A., Campuzano, Victoria
Tipo de recurso: artículo
Fecha de publicación:2010
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6524
Acceso en línea:http://hdl.handle.net/20.500.12105/6524
Access Level:acceso abierto
Palabra clave:WILLIAMS-BEUREN-SYNDROME
GTF2IRD1
DELETIONS
MICE
MECHANISMS
PHENOTYPE
GENES
GTF21
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repository_id_str
spelling Essential role of the N-terminal region of TFII-I in viability and behaviorLucena, JaumePezzi, SusanaAso, EsterValero, Maria C.Carreiro, CandelasDubus, PierreSampaio, AdrianaSegura, MariaBarthelemy, IsabelZindel, Marc Y.Sousa, NunoBarbero, Jose L.Maldonado, RafaelPerez-Jurado, Luis A.Campuzano, VictoriaWILLIAMS-BEUREN-SYNDROMEGTF2IRD1DELETIONSMICEMECHANISMSPHENOTYPEGENESGTF21Background: GTF2I codes for a general intrinsic transcription factor and calcium channel regulator TFII-I, with high and ubiquitous expression, and a strong candidate for involvement in the morphological and neuro-developmental anomalies of the Williams-Beuren syndrome (WBS). WBS is a genetic disorder due to a recurring deletion of about 1,551,83 Mb containing 25-28 genes in chromosome band 7q11.23 including GTF2I. Completed homozygous loss of either the Gtf2i or Gtf2ird1 function in mice provided additional evidence for the involvement of both genes in the craniofacial and cognitive phenotype. Unfortunately nothing is now about the behavioral characterization of heterozygous mice. Methods: By gene targeting we have generated a mutant mice with a deletion of the first 140 amino-acids of TFII-I. mRNA and protein expression analysis were used to document the effect of the study deletion. We performed behavioral characterization of heterozygous mutant mice to document in vivo implications of TFII-I in the cognitive profile of WBS patients. Results: Homozygous and heterozygous mutant mice exhibit craniofacial alterations, most clearly represented in homozygous condition. Behavioral test demonstrate that heterozygous mutant mice exhibit some neurobehavioral alterations and hyperacusis or odynacusis that could be associated with specific features of WBS phenotype. Homozygous mutant mice present highly compromised embryonic viability and fertility. Regarding cellular model, we documented a retarded growth in heterozygous MEFs respect to homozygous or wild-type MEFs. Conclusion: Our data confirm that, although additive effects of haploinsufficiency at several genes may contribute to the full craniofacial or neurocognitive features of WBS, correct expression of GTF2I is one of the main players. In addition, these findings show that the deletion of the fist 140 amino-acids of TFII-I altered it correct function leading to a clear phenotype, at both levels, at the cellular model and at the in vivo model.BioMed Central (BMC)Ministerio de Sanidad, Servicios Sociales e Igualdad (España)Ministerio de Educación y Ciencia (España)Unión Europea20182018-10-2520102010-01-0120102010-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/6524reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/65242026-06-12T12:43:37Z
dc.title.none.fl_str_mv Essential role of the N-terminal region of TFII-I in viability and behavior
title Essential role of the N-terminal region of TFII-I in viability and behavior
spellingShingle Essential role of the N-terminal region of TFII-I in viability and behavior
Lucena, Jaume
WILLIAMS-BEUREN-SYNDROME
GTF2IRD1
DELETIONS
MICE
MECHANISMS
PHENOTYPE
GENES
GTF21
title_short Essential role of the N-terminal region of TFII-I in viability and behavior
title_full Essential role of the N-terminal region of TFII-I in viability and behavior
title_fullStr Essential role of the N-terminal region of TFII-I in viability and behavior
title_full_unstemmed Essential role of the N-terminal region of TFII-I in viability and behavior
title_sort Essential role of the N-terminal region of TFII-I in viability and behavior
dc.creator.none.fl_str_mv Lucena, Jaume
Pezzi, Susana
Aso, Ester
Valero, Maria C.
Carreiro, Candelas
Dubus, Pierre
Sampaio, Adriana
Segura, Maria
Barthelemy, Isabel
Zindel, Marc Y.
Sousa, Nuno
Barbero, Jose L.
Maldonado, Rafael
Perez-Jurado, Luis A.
Campuzano, Victoria
author Lucena, Jaume
author_facet Lucena, Jaume
Pezzi, Susana
Aso, Ester
Valero, Maria C.
Carreiro, Candelas
Dubus, Pierre
Sampaio, Adriana
Segura, Maria
Barthelemy, Isabel
Zindel, Marc Y.
Sousa, Nuno
Barbero, Jose L.
Maldonado, Rafael
Perez-Jurado, Luis A.
Campuzano, Victoria
author_role author
author2 Pezzi, Susana
Aso, Ester
Valero, Maria C.
Carreiro, Candelas
Dubus, Pierre
Sampaio, Adriana
Segura, Maria
Barthelemy, Isabel
Zindel, Marc Y.
Sousa, Nuno
Barbero, Jose L.
Maldonado, Rafael
Perez-Jurado, Luis A.
Campuzano, Victoria
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Sanidad, Servicios Sociales e Igualdad (España)
Ministerio de Educación y Ciencia (España)
Unión Europea
dc.subject.none.fl_str_mv WILLIAMS-BEUREN-SYNDROME
GTF2IRD1
DELETIONS
MICE
MECHANISMS
PHENOTYPE
GENES
GTF21
topic WILLIAMS-BEUREN-SYNDROME
GTF2IRD1
DELETIONS
MICE
MECHANISMS
PHENOTYPE
GENES
GTF21
description Background: GTF2I codes for a general intrinsic transcription factor and calcium channel regulator TFII-I, with high and ubiquitous expression, and a strong candidate for involvement in the morphological and neuro-developmental anomalies of the Williams-Beuren syndrome (WBS). WBS is a genetic disorder due to a recurring deletion of about 1,551,83 Mb containing 25-28 genes in chromosome band 7q11.23 including GTF2I. Completed homozygous loss of either the Gtf2i or Gtf2ird1 function in mice provided additional evidence for the involvement of both genes in the craniofacial and cognitive phenotype. Unfortunately nothing is now about the behavioral characterization of heterozygous mice. Methods: By gene targeting we have generated a mutant mice with a deletion of the first 140 amino-acids of TFII-I. mRNA and protein expression analysis were used to document the effect of the study deletion. We performed behavioral characterization of heterozygous mutant mice to document in vivo implications of TFII-I in the cognitive profile of WBS patients. Results: Homozygous and heterozygous mutant mice exhibit craniofacial alterations, most clearly represented in homozygous condition. Behavioral test demonstrate that heterozygous mutant mice exhibit some neurobehavioral alterations and hyperacusis or odynacusis that could be associated with specific features of WBS phenotype. Homozygous mutant mice present highly compromised embryonic viability and fertility. Regarding cellular model, we documented a retarded growth in heterozygous MEFs respect to homozygous or wild-type MEFs. Conclusion: Our data confirm that, although additive effects of haploinsufficiency at several genes may contribute to the full craniofacial or neurocognitive features of WBS, correct expression of GTF2I is one of the main players. In addition, these findings show that the deletion of the fist 140 amino-acids of TFII-I altered it correct function leading to a clear phenotype, at both levels, at the cellular model and at the in vivo model.
publishDate 2010
dc.date.none.fl_str_mv 2010
2010-01-01
2010
2010-01-01
2018
2018-10-25
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/6524
url http://hdl.handle.net/20.500.12105/6524
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
application/vnd.openxmlformats-officedocument.wordprocessingml.document
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central (BMC)
publisher.none.fl_str_mv BioMed Central (BMC)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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