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dc.contributor.author | Salminen, Aaro V. | |
dc.contributor.author | Garrett, Lillian | |
dc.contributor.author | Schormair, Barbara | |
dc.contributor.author | Rozman, Jan | |
dc.contributor.author | Giesert, Florian | |
dc.contributor.author | Niedermeier, Kristina M. | |
dc.contributor.author | Becker, Lore | |
dc.contributor.author | Rathkolb, Birgit | |
dc.contributor.author | Racz, Ildiko | |
dc.contributor.author | Klingenspor, Martin | |
dc.contributor.author | Klopstock, Thomas | |
dc.contributor.author | Wolf, Eckhard | |
dc.contributor.author | Zimmer, Andreas | |
dc.contributor.author | Gailus-Durner, Valerie | |
dc.contributor.author | Torres, Miguel | |
dc.contributor.author | Fuchs, Helmut. | |
dc.contributor.author | Hrabe de Angelis, Martin | |
dc.contributor.author | Wurst, Wolfgang | |
dc.contributor.author | Hoelter, Sabine M | |
dc.contributor.author | Winkelmann, Juliane | |
dc.date.accessioned | 2018-10-19T08:00:44Z | |
dc.date.available | 2018-10-19T08:00:44Z | |
dc.date.issued | 2017 | |
dc.identifier | ISI:000406796600005 | |
dc.identifier.citation | Dis Model Mech. 2017; 10(8):981-991 | |
dc.identifier.issn | 1754-8403 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6500 | |
dc.description.abstract | MEIS1 encodes a developmental transcription factor and has been linked to restless legs syndrome (RLS) in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and has a substantial impact on the quality of life of patients. In genome-wide association studies, MEIS1 has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation. Therefore, haploinsufficiency of Meis1 could be the system with the most potential for modeling RLS in animals. We used heterozygous Meis1-knockout mice to study the effects of Meis1 haploinsufficiency on mouse behavioral and neurological phenotypes, and to relate the findings to human RLS. We exposed the Meis1-deficient mice to assays of motor, sensorimotor and cognitive ability, and assessed the effect of a dopaminergic receptor 2/3 agonist commonly used in the treatment of RLS. The mutant mice showed a pattern of circadian hyperactivity, which is compatible with human RLS. Moreover, we discovered a replicable prepulse inhibition (PPI) deficit in the Meis1-deficient animals. In addition, these mice were hyposensitive to the PPI-reducing effect of the dopaminergic receptor agonist, highlighting a role of Meis1 in the dopaminergic system. Other reported phenotypes include enhanced social recognition at an older age that was not related to alterations in adult olfactory bulb neurogenesis previously shown to be implicated in this behavior. In conclusion, the Meis1-deficient mice fulfill some of the hallmarks of an RLS animal model, and revealed the role of Meis1 in sensorimotor gating and in the dopaminergic systems modulating it. | |
dc.description.sponsorship | A.V.S. was supported by the Emil Aaltonen Foundation, Tampere, Finland (Emil Aaltosen Saatio). J.W. and M.T. were partly funded by the European Commission through an ERA-NET NEURON grant. This work has been funded by the German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung) to the GMC (Infrafrontier grant 01KX1012), to the German Center for Diabetes Research (DZD e.V.) and through the Integrated Network MitoPD (Mitochondrial endophenotypes of Morbus Parkinson), under the auspices of the e:Med Programme (grant 031A430E), as well as by the Helmholtz Portfolio Theme `Supercomputing and Modelling for the Human Brain' (SMHB) to W.W. This work was also supported by the German Science Foundation Collaborative Research Centre (CRC) (Deutsche Forschungsgemeinschaft) 870. | |
dc.language.iso | eng | |
dc.publisher | The Company of Biologists | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Meis1 | |
dc.subject | Prepulse inhibition | |
dc.subject | Restless legs syndrome | |
dc.subject | Sensorimotor system | |
dc.subject | Mouse model | |
dc.subject | Pramipexole | |
dc.subject | RESTLESS LEGS SYNDROME | |
dc.subject | GENOME-WIDE ASSOCIATION | |
dc.subject | PREPULSE INHIBITION | |
dc.subject | EXPRESSION LEVELS | |
dc.subject | RISK | |
dc.subject | GENES | |
dc.subject | SLEEP | |
dc.subject | PATHOPHYSIOLOGY | |
dc.subject | HOMEOPROTEINS | |
dc.subject | NEUROGENESIS | |
dc.title | Meis1: effects on motor phenotypes and the sensorimotor system in mice | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 28645892 | |
dc.format.volume | 10 | |
dc.format.page | 981-991 | |
dc.identifier.doi | 10.1242/dmm.030080 | |
dc.contributor.funder | Emil Aaltosen Säätiö (Finlandia) | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Federal Ministry of Education & Research (Alemania) | |
dc.contributor.funder | Deutsche Forschungsgemeinschaft (Alemania) | |
dc.description.peerreviewed | Sí | |
dc.identifier.e-issn | 1754-8411 | |
dc.relation.publisherversion | https://doi.org/10.1242/dmm.030080 | |
dc.identifier.journal | Disease Models and Mechanisms | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Control Genético del Desarrollo y Regeneración de Órganos | |
dc.repisalud.institucion | CNIC | |
dc.rights.accessRights | open access | es_ES |