Animal models of RLS phenotypes

Richard P. Allen, Nathan C. Donelson, Byron Jones, Yuqing Li, Mauro Manconi, David B. Rye, Subhabrata Sanyal, Juliane Winkelmann

Research output: Contribution to journalReview article

8 Citations (Scopus)

Abstract

Restless legs syndrome (RLS) is a complex disorder that involves sensory and motor systems. The major pathophysiology of RLS is low iron concentration in the substantia nigra containing the cell bodies of dopamine neurons that project to the striatum, an area that is crucial for modulating movement. People who have RLS often present with normal iron values outside the brain; recent studies implicate several genes are involved in the syndrome. Like most complex diseases, animal models usually do not faithfully capture the full phenotypic spectrum of “disease,” which is a uniquely human construct. Nonetheless, animal models have proven useful in helping to unravel the complex pathophysiology of diseases such as RLS and suggesting novel treatment paradigms. For example, hypothesis-independent genome-wide association studies (GWAS) have identified several genes as increasing the risk for RLS, including BTBD9. Independently, the murine homolog Btbd9 was identified as a candidate gene for iron regulation in the midbrain in mice. The relevance of the phenotype of another of the GWAS identified genes, MEIS1, has also been explored. The role of Btbd9 in iron regulation and RLS-like behaviors has been further evaluated in mice carrying a null mutation of the gene and in fruit flies when the BTBD9 protein is degraded. The BTBD9 and MEIS1 stories originate from human GWAS research, supported by work in a genetic reference population of mice (forward genetics) and further verified in mice, fish flies, and worms. Finally, the role of genetics is further supported by an inbred mouse strain that displays many of the phenotypic characteristics of RLS. The role of animal models of RLS phenotypes is also extended to include periodic limb movements.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalSleep Medicine
Volume31
DOIs
StatePublished - Mar 1 2017

Fingerprint

Restless Legs Syndrome
Animal Models
Phenotype
Genome-Wide Association Study
Iron
Genes
Diptera
Sensation Disorders
Animal Disease Models
Inbred Strains Mice
Dopaminergic Neurons
Population Genetics
Human Genome
Substantia Nigra
Mesencephalon
Fruit
Fishes
Reference Values
Extremities
Mutation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Allen, R. P., Donelson, N. C., Jones, B., Li, Y., Manconi, M., Rye, D. B., ... Winkelmann, J. (2017). Animal models of RLS phenotypes. Sleep Medicine, 31, 23-28. https://doi.org/10.1016/j.sleep.2016.08.002

Animal models of RLS phenotypes. / Allen, Richard P.; Donelson, Nathan C.; Jones, Byron; Li, Yuqing; Manconi, Mauro; Rye, David B.; Sanyal, Subhabrata; Winkelmann, Juliane.

In: Sleep Medicine, Vol. 31, 01.03.2017, p. 23-28.

Research output: Contribution to journalReview article

Allen, RP, Donelson, NC, Jones, B, Li, Y, Manconi, M, Rye, DB, Sanyal, S & Winkelmann, J 2017, 'Animal models of RLS phenotypes', Sleep Medicine, vol. 31, pp. 23-28. https://doi.org/10.1016/j.sleep.2016.08.002
Allen RP, Donelson NC, Jones B, Li Y, Manconi M, Rye DB et al. Animal models of RLS phenotypes. Sleep Medicine. 2017 Mar 1;31:23-28. https://doi.org/10.1016/j.sleep.2016.08.002
Allen, Richard P. ; Donelson, Nathan C. ; Jones, Byron ; Li, Yuqing ; Manconi, Mauro ; Rye, David B. ; Sanyal, Subhabrata ; Winkelmann, Juliane. / Animal models of RLS phenotypes. In: Sleep Medicine. 2017 ; Vol. 31. pp. 23-28.
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