PuSH - Publication Server of Helmholtz Zentrum München

Leu, C.-L. ; Lam, D. ; Salminen, A.V. ; Wefers, B. ; Becker, L. ; Garrett, L. ; Rozman, J. ; Wurst, W. ; Hrabě de Angelis, M. ; Hölter, S.M. ; Winkelmann, J. ; Williams, R.H.

A patient-enriched MEIS1 coding variant causes a restless legs syndrome-like phenotype in mice.

Sleep 47:zsae015 (2024)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Restless legs syndrome (RLS) is a neurological disorder characterized by uncomfortable or unpleasant sensations in the legs during rest periods. To relieve these sensations, patients move their legs, causing sleep disruption. While the pathogenesis of RLS has yet to be resolved, there is a strong genetic association to the MEIS1 gene. A missense variant in MEIS1 is enriched 7-fold in RLS patients compared to non-affected individuals. We generated a mouse line carrying this mutation (p.Arg272His/c.815G>A), referred to herein as Meis1R272H/R272H (Meis1 point mutation), to determine whether it would phenotypically resemble RLS. As women are more prone to RLS, driven partly by an increased risk of developing RLS during pregnancy, we focussed on female homozygous mice. We evaluated RLS-related outcomes, particularly sensorimotor behavior and sleep, in young and aged mice. Compared to non-carrier littermates, homozygous mice displayed very few differences. Significant hyperactivity occurred before the lights-on (rest) period in aged female mice, reflecting the age-dependent incidence of RLS. Sensory experiments involving tactile feedback (rotorod, wheel running, and hotplate) were only marginally different. Overall, RLS-like phenomena were not recapitulated except for the increased wake activity prior to rest. This is likely due to the focus on young mice. Nevertheless, the Meis1R272H mouse line is a potentially useful RLS model, carrying a clinically relevant variant and showing an age-dependent phenotype.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Meis1 ; Mouse Model ; Restless Legs Syndrome; Genome-wide Association; Sleep; Prevalence; Symptoms; Risk; Iron; Epidemiology; Population; System; Onset
ISSN (print) / ISBN 0161-8105
e-ISSN 1550-9109
Journal Sleep
Quellenangaben Volume: 47, Issue: 5, Pages: , Article Number: zsae015 Supplement: ,
Publisher American Academy of Sleep Medicine and the Sleep Research Society
Publishing Place Journals Dept, 2001 Evans Rd, Cary, Nc 27513 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
Grants Internal funding (Helmholtz Munich)
German Federal Ministry of Education and Research
German Center for Diabetes Research (DZD)
ERC under the European Union