2026-08-29T14:04:38Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65002024-09-27T09:05:28Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Salminen, Aaro V.
author
Garrett, Lillian
author
Schormair, Barbara
author
Rozman, Jan
author
Giesert, Florian
author
Niedermeier, Kristina M.
author
Becker, Lore
author
Rathkolb, Birgit
author
Racz, Ildiko
author
Klingenspor, Martin
author
Klopstock, Thomas
author
Wolf, Eckhard
author
Zimmer, Andreas
author
Gailus-Durner, Valerie
author
Torres, Miguel
author
Fuchs, Helmut.
author
Hrabe de Angelis, Martin
author
Wurst, Wolfgang
author
Hoelter, Sabine M
author
Winkelmann, Juliane
funder
Emil Aaltosen Säätiö (Finlandia)
funder
Unión Europea. Comisión Europea
funder
Federal Ministry of Education & Research (Alemania)
funder
Deutsche Forschungsgemeinschaft (Alemania)
2018-10-19T08:00:44Z
2018-10-19T08:00:44Z
2017
Dis Model Mech. 2017; 10(8):981-991
10.1242/dmm.030080
1754-8411
1754-8403
Disease Models and Mechanisms
28645892
http://hdl.handle.net/20.500.12105/6500
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.
eng
Meis1
Prepulse inhibition
Restless legs syndrome
Sensorimotor system
Mouse model
Pramipexole
RESTLESS LEGS SYNDROME
GENOME-WIDE ASSOCIATION
PREPULSE INHIBITION
EXPRESSION LEVELS
RISK
GENES
SLEEP
PATHOPHYSIOLOGY
HOMEOPROTEINS
NEUROGENESIS
Meis1: effects on motor phenotypes and the sensorimotor system in mice
journal article
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