Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells

Castro-Torres, Rubén Darío; Olloquequi, Jordi; Ettcheto Arriola, Miren; Caruana, Pablo; Steele, Luke; Leighton, Kyra-Mae; Ureña Bares, Jesús Mariano; Beas Zárate, Carlos; Camins Espuny, Antoni; Verdaguer Cardona, Ester; Auladell i Costa, M. Carme

Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells

(1) Background: The c-Jun-NH2-terminal protein kinase (JNK) is a mitogen-activated protein kinase involved in regulating physiological processes in the central nervous system. However, the dual genetic deletion of Mkk4 and Mkk7 (upstream activators of JNK) in adult mice is not reported. The aim of t...

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Autores:	Castro-Torres, Rubén Darío, Olloquequi, Jordi, Ettcheto Arriola, Miren, Caruana, Pablo, Steele, Luke, Leighton, Kyra-Mae, Ureña Bares, Jesús Mariano, Beas Zárate, Carlos, Camins Espuny, Antoni, Verdaguer Cardona, Ester, Auladell i Costa, M. Carme
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2021
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/181376
Acceso en línea:	https://hdl.handle.net/2445/181376
Access Level:	acceso abierto
Palabra clave:	Hipocamp (Cervell) Proteïnes quinases Hippocampus (Brain) Protein kinases

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spelling	Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule CellsCastro-Torres, Rubén DaríoOlloquequi, JordiEttcheto Arriola, MirenCaruana, PabloSteele, LukeLeighton, Kyra-MaeUreña Bares, Jesús MarianoBeas Zárate, CarlosCamins Espuny, AntoniVerdaguer Cardona, EsterAuladell i Costa, M. CarmeHipocamp (Cervell)Proteïnes quinasesHippocampus (Brain)Protein kinases(1) Background: The c-Jun-NH2-terminal protein kinase (JNK) is a mitogen-activated protein kinase involved in regulating physiological processes in the central nervous system. However, the dual genetic deletion of Mkk4 and Mkk7 (upstream activators of JNK) in adult mice is not reported. The aim of this study was to induce the genetic deletion of Mkk4/Mkk7 in adult mice and analyze their effect in hippocampal neurogenesis. (2) Methods: To achieve this goal, Actin-CreERT2 (Cre+/−), Mkk4flox/flox, Mkk7flox/flox mice were created. The administration of tamoxifen in these 2-month-old mice induced the gene deletion (Actin-CreERT2 (Cre+/−), Mkk4∆/∆, Mkk7∆/∆ genotype), which was verified by PCR, Western blot, and immunohistochemistry techniques. (3) Results: The levels of MKK4/MKK7 at 7 and 14 days after tamoxifen administration were not eliminated totally in CNS, unlike what happens in the liver and heart. These data could be correlated with the high levels of these proteins in CNS. In the hippocampus, the deletion of Mkk4/Mkk7 induced a misalignment position of immature hippocampal neurons together with alterations in their dendritic architecture pattern and maturation process jointly to the diminution of JNK phosphorylation. (4) Conclusion: All these data supported that the MKK4/MKK7-JNK pathway has a role in adult neurogenic activity.MDPI2021202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion18 p.application/pdfhttps://hdl.handle.net/2445/181376Articles publicats en revistes (Bioquímica i Fisiologia)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/10.3390/ijms22179545International Journal of Molecular Sciences, 2021, vol. 22, num. 17, p. 9545https://doi.org/10.3390/ijms22179545cc-by (c) Castro-Torres, Rubén Darío et al., 2021https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1813762026-05-29T05:05:01Z
dc.title.none.fl_str_mv	Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells
title	Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells
spellingShingle	Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells Castro-Torres, Rubén Darío Hipocamp (Cervell) Proteïnes quinases Hippocampus (Brain) Protein kinases
title_short	Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells
title_full	Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells
title_fullStr	Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells
title_full_unstemmed	Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells
title_sort	Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells
dc.creator.none.fl_str_mv	Castro-Torres, Rubén Darío Olloquequi, Jordi Ettcheto Arriola, Miren Caruana, Pablo Steele, Luke Leighton, Kyra-Mae Ureña Bares, Jesús Mariano Beas Zárate, Carlos Camins Espuny, Antoni Verdaguer Cardona, Ester Auladell i Costa, M. Carme
author	Castro-Torres, Rubén Darío
author_facet	Castro-Torres, Rubén Darío Olloquequi, Jordi Ettcheto Arriola, Miren Caruana, Pablo Steele, Luke Leighton, Kyra-Mae Ureña Bares, Jesús Mariano Beas Zárate, Carlos Camins Espuny, Antoni Verdaguer Cardona, Ester Auladell i Costa, M. Carme
author_role	author
author2	Olloquequi, Jordi Ettcheto Arriola, Miren Caruana, Pablo Steele, Luke Leighton, Kyra-Mae Ureña Bares, Jesús Mariano Beas Zárate, Carlos Camins Espuny, Antoni Verdaguer Cardona, Ester Auladell i Costa, M. Carme
author2_role	author author author author author author author author author author
dc.subject.none.fl_str_mv	Hipocamp (Cervell) Proteïnes quinases Hippocampus (Brain) Protein kinases
topic	Hipocamp (Cervell) Proteïnes quinases Hippocampus (Brain) Protein kinases
description	(1) Background: The c-Jun-NH2-terminal protein kinase (JNK) is a mitogen-activated protein kinase involved in regulating physiological processes in the central nervous system. However, the dual genetic deletion of Mkk4 and Mkk7 (upstream activators of JNK) in adult mice is not reported. The aim of this study was to induce the genetic deletion of Mkk4/Mkk7 in adult mice and analyze their effect in hippocampal neurogenesis. (2) Methods: To achieve this goal, Actin-CreERT2 (Cre+/−), Mkk4flox/flox, Mkk7flox/flox mice were created. The administration of tamoxifen in these 2-month-old mice induced the gene deletion (Actin-CreERT2 (Cre+/−), Mkk4∆/∆, Mkk7∆/∆ genotype), which was verified by PCR, Western blot, and immunohistochemistry techniques. (3) Results: The levels of MKK4/MKK7 at 7 and 14 days after tamoxifen administration were not eliminated totally in CNS, unlike what happens in the liver and heart. These data could be correlated with the high levels of these proteins in CNS. In the hippocampus, the deletion of Mkk4/Mkk7 induced a misalignment position of immature hippocampal neurons together with alterations in their dendritic architecture pattern and maturation process jointly to the diminution of JNK phosphorylation. (4) Conclusion: All these data supported that the MKK4/MKK7-JNK pathway has a role in adult neurogenic activity.
publishDate	2021
dc.date.none.fl_str_mv	2021 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/2445/181376
url	https://hdl.handle.net/2445/181376
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/10.3390/ijms22179545 International Journal of Molecular Sciences, 2021, vol. 22, num. 17, p. 9545 https://doi.org/10.3390/ijms22179545
dc.rights.none.fl_str_mv	cc-by (c) Castro-Torres, Rubén Darío et al., 2021 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) Castro-Torres, Rubén Darío et al., 2021 https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	18 p. application/pdf
dc.publisher.none.fl_str_mv	MDPI
publisher.none.fl_str_mv	MDPI
dc.source.none.fl_str_mv	Articles publicats en revistes (Bioquímica i Fisiologia) 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
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score	15,81155

Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells

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