Behavioural and functional characterization of Kν10.1 (Eag1) knockout mice

Kv10.1 (Eag1), member of the Kv10 family of voltage-gated potassium channels, is preferentially expressed in adult brain. The aim of the present study was to unravel the functional role of Kv10.1 in the brain by generating knockout mice, where the voltage sensor and pore region of Kv10.1 were remove...

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Autores: Ufartes, Roser, Schneider, Tomasz, Sünke Mortensen, Lena, Juan Romero, Camino de, Hentrich, Klaus, Knoetgen, Hendrik, Beilinson, Vadim, Moebius, Wiebke, Tarabykin, Victor, Alves, Frauke, Pardo, Luis A., Rawlins, J. Nicholas P., Stuehmer, Walter
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2013
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/288791
Acesso em linha:http://hdl.handle.net/10261/288791
Access Level:Acceso aberto
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spelling Behavioural and functional characterization of Kν10.1 (Eag1) knockout miceUfartes, RoserSchneider, TomaszSünke Mortensen, LenaJuan Romero, Camino deHentrich, KlausKnoetgen, HendrikBeilinson, VadimMoebius, WiebkeTarabykin, VictorAlves, FraukePardo, Luis A.Rawlins, J. Nicholas P.Stuehmer, WalterKv10.1 (Eag1), member of the Kv10 family of voltage-gated potassium channels, is preferentially expressed in adult brain. The aim of the present study was to unravel the functional role of Kv10.1 in the brain by generating knockout mice, where the voltage sensor and pore region of Kv10.1 were removed to render non-functional proteins through deletion of exon 7 of the KCNH1 gene using the ‘3 Lox P strategy’. Kv10.1-deficient mice show no obvious alterations during embryogenesis and develop normally to adulthood; cortex, hippocampus and cerebellum appear anatomically normal. Other tests, including general health screen, sensorimotor functioning and gating, anxiety, social behaviour, learning and memory did not show any functional aberrations in Kv10.1 null mice. Kv10.1 null mice display mild hyperactivity and longer-lasting haloperidol-induced catalepsy, but there was no difference between genotypes in amphetamine sensitization and withdrawal, reactivity to apomorphine and haloperidol in the prepulse inhibition tests or to antidepressants in the haloperidol-induced catalepsy. Furthermore, electrical properties of Kv10.1 in cerebellar Purkinje cells did not show any difference between genotypes. Bearing in mind that Kv10.1 is overexpressed in over 70% of all human tumours and that its inhibition leads to a reduced tumour cell proliferation, the fact that deletion of Kv10.1 does not show a marked phenotype is a prerequisite for utilizing Kv10.1 blocking and/or reduction techniques, such as siRNA, to treat cancer.This work was supported by the Max Planck Society (Tandem Grant). Funding to pay the Open Access publication charges for this article was provided by Max Planck Society.Peer reviewedOxford University PressMax Planck SocietyConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232013info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/288791reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésHuman Molecular Geneticshttps://doi.org/10.1093/hmg/ddt076Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2887912026-05-22T06:33:51Z
dc.title.none.fl_str_mv Behavioural and functional characterization of Kν10.1 (Eag1) knockout mice
title Behavioural and functional characterization of Kν10.1 (Eag1) knockout mice
spellingShingle Behavioural and functional characterization of Kν10.1 (Eag1) knockout mice
Ufartes, Roser
title_short Behavioural and functional characterization of Kν10.1 (Eag1) knockout mice
title_full Behavioural and functional characterization of Kν10.1 (Eag1) knockout mice
title_fullStr Behavioural and functional characterization of Kν10.1 (Eag1) knockout mice
title_full_unstemmed Behavioural and functional characterization of Kν10.1 (Eag1) knockout mice
title_sort Behavioural and functional characterization of Kν10.1 (Eag1) knockout mice
dc.creator.none.fl_str_mv Ufartes, Roser
Schneider, Tomasz
Sünke Mortensen, Lena
Juan Romero, Camino de
Hentrich, Klaus
Knoetgen, Hendrik
Beilinson, Vadim
Moebius, Wiebke
Tarabykin, Victor
Alves, Frauke
Pardo, Luis A.
Rawlins, J. Nicholas P.
Stuehmer, Walter
author Ufartes, Roser
author_facet Ufartes, Roser
Schneider, Tomasz
Sünke Mortensen, Lena
Juan Romero, Camino de
Hentrich, Klaus
Knoetgen, Hendrik
Beilinson, Vadim
Moebius, Wiebke
Tarabykin, Victor
Alves, Frauke
Pardo, Luis A.
Rawlins, J. Nicholas P.
Stuehmer, Walter
author_role author
author2 Schneider, Tomasz
Sünke Mortensen, Lena
Juan Romero, Camino de
Hentrich, Klaus
Knoetgen, Hendrik
Beilinson, Vadim
Moebius, Wiebke
Tarabykin, Victor
Alves, Frauke
Pardo, Luis A.
Rawlins, J. Nicholas P.
Stuehmer, Walter
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Max Planck Society
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Kv10.1 (Eag1), member of the Kv10 family of voltage-gated potassium channels, is preferentially expressed in adult brain. The aim of the present study was to unravel the functional role of Kv10.1 in the brain by generating knockout mice, where the voltage sensor and pore region of Kv10.1 were removed to render non-functional proteins through deletion of exon 7 of the KCNH1 gene using the ‘3 Lox P strategy’. Kv10.1-deficient mice show no obvious alterations during embryogenesis and develop normally to adulthood; cortex, hippocampus and cerebellum appear anatomically normal. Other tests, including general health screen, sensorimotor functioning and gating, anxiety, social behaviour, learning and memory did not show any functional aberrations in Kv10.1 null mice. Kv10.1 null mice display mild hyperactivity and longer-lasting haloperidol-induced catalepsy, but there was no difference between genotypes in amphetamine sensitization and withdrawal, reactivity to apomorphine and haloperidol in the prepulse inhibition tests or to antidepressants in the haloperidol-induced catalepsy. Furthermore, electrical properties of Kv10.1 in cerebellar Purkinje cells did not show any difference between genotypes. Bearing in mind that Kv10.1 is overexpressed in over 70% of all human tumours and that its inhibition leads to a reduced tumour cell proliferation, the fact that deletion of Kv10.1 does not show a marked phenotype is a prerequisite for utilizing Kv10.1 blocking and/or reduction techniques, such as siRNA, to treat cancer.
publishDate 2013
dc.date.none.fl_str_mv 2013
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/10261/288791
url http://hdl.handle.net/10261/288791
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Human Molecular Genetics
https://doi.org/10.1093/hmg/ddt076
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 Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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