Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.

Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alt...

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Autores: Alén, Francisco, Gómez-Redondo, Isabel, Rivera, Patricia, Suárez, Juan, Ramos-Ibeas, Priscila, Pericuesta, Eva, Fernández-González, Raul, Perez-Cerezales, Serafín, Horiuchi, Keiko, Orio, Laura, Rodriguez de Fonseca, Fernando, Gutiérrez-Adán, Alfonso
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17892
Acceso en línea:http://hdl.handle.net/20.500.12105/17892
Access Level:acceso abierto
Palabra clave:U12 introns
Zrsr1
Behavior
Cell proliferation
Hypothalamus
Neurogenesis
Social interaction
Alternative Splicing
Animals
Behavior, Animal
Cell Line, Tumor
Cell Proliferation
Cell Survival
Gene Expression Regulation
Humans
Introns
Mice
Mice, Knockout
Mutation
Phenotype
RNA Splicing
RNA Splicing Factors
Social Behavior
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repository_id_str
spelling Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.Alén, FranciscoGómez-Redondo, IsabelRivera, PatriciaSuárez, JuanRamos-Ibeas, PriscilaPericuesta, EvaFernández-González, RaulPerez-Cerezales, SerafínHoriuchi, KeikoOrio, LauraRodriguez de Fonseca, FernandoGutiérrez-Adán, AlfonsoU12 intronsZrsr1BehaviorCell proliferationHypothalamusNeurogenesisSocial interactionAlternative SplicingAnimalsBehavior, AnimalCell Line, TumorCell ProliferationCell SurvivalGene Expression RegulationHumansHypothalamusIntronsMiceMice, KnockoutMutationNeurogenesisPhenotypeRNA SplicingRNA Splicing FactorsSocial BehaviorMutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior.20242024-02-1020192019-07-1920192019-07-19research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/17892reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/178922026-06-12T12:43:37Z
dc.title.none.fl_str_mv Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.
title Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.
spellingShingle Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.
Alén, Francisco
U12 introns
Zrsr1
Behavior
Cell proliferation
Hypothalamus
Neurogenesis
Social interaction
Alternative Splicing
Animals
Behavior, Animal
Cell Line, Tumor
Cell Proliferation
Cell Survival
Gene Expression Regulation
Humans
Hypothalamus
Introns
Mice
Mice, Knockout
Mutation
Neurogenesis
Phenotype
RNA Splicing
RNA Splicing Factors
Social Behavior
title_short Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.
title_full Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.
title_fullStr Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.
title_full_unstemmed Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.
title_sort Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.
dc.creator.none.fl_str_mv Alén, Francisco
Gómez-Redondo, Isabel
Rivera, Patricia
Suárez, Juan
Ramos-Ibeas, Priscila
Pericuesta, Eva
Fernández-González, Raul
Perez-Cerezales, Serafín
Horiuchi, Keiko
Orio, Laura
Rodriguez de Fonseca, Fernando
Gutiérrez-Adán, Alfonso
author Alén, Francisco
author_facet Alén, Francisco
Gómez-Redondo, Isabel
Rivera, Patricia
Suárez, Juan
Ramos-Ibeas, Priscila
Pericuesta, Eva
Fernández-González, Raul
Perez-Cerezales, Serafín
Horiuchi, Keiko
Orio, Laura
Rodriguez de Fonseca, Fernando
Gutiérrez-Adán, Alfonso
author_role author
author2 Gómez-Redondo, Isabel
Rivera, Patricia
Suárez, Juan
Ramos-Ibeas, Priscila
Pericuesta, Eva
Fernández-González, Raul
Perez-Cerezales, Serafín
Horiuchi, Keiko
Orio, Laura
Rodriguez de Fonseca, Fernando
Gutiérrez-Adán, Alfonso
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv U12 introns
Zrsr1
Behavior
Cell proliferation
Hypothalamus
Neurogenesis
Social interaction
Alternative Splicing
Animals
Behavior, Animal
Cell Line, Tumor
Cell Proliferation
Cell Survival
Gene Expression Regulation
Humans
Hypothalamus
Introns
Mice
Mice, Knockout
Mutation
Neurogenesis
Phenotype
RNA Splicing
RNA Splicing Factors
Social Behavior
topic U12 introns
Zrsr1
Behavior
Cell proliferation
Hypothalamus
Neurogenesis
Social interaction
Alternative Splicing
Animals
Behavior, Animal
Cell Line, Tumor
Cell Proliferation
Cell Survival
Gene Expression Regulation
Humans
Hypothalamus
Introns
Mice
Mice, Knockout
Mutation
Neurogenesis
Phenotype
RNA Splicing
RNA Splicing Factors
Social Behavior
description Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-07-19
2019
2019-07-19
2024
2024-02-10
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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/20.500.12105/17892
url http://hdl.handle.net/20.500.12105/17892
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
Attribution 4.0 International
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
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
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
_version_ 1869407751638089728
score 15,811543

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