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Author Notes:

Correspondence: Subhabrata Sanyal, Room No. 444, 615 Michael St., NE, Whitehead Building, Emory University, Atlanta, GA 30322; Email: ssanya2@emory.edu; Phone: (404) 727 1250; Fax: (404) 727 6256

Acknowledgments: We thank members of the Betarbet, Jinnah, Rye and Sanyal laboratory for technical assistance, comments and criticisms, Diana Woodall and Sonya Patel for initial characterization of fly phenotypes, Paul Shaw for sharing his sleep analysis software, Bjorn Brembs for the Buridan analysis software and Wendi Neckameyer for sharing the anti-TH antibody.


Research Funding:

This work is supported by a FIRST fellowship and a Neurology NIH T32 fellowship to A.F. and Emory Neuroscience Initiative, Sleep Research Society and Restless Legs Foundation grants to S.S.

Sleep fragmentation and motor restlessness in a Drosophila model of Restless Legs Syndrome


Journal Title:

Current Biology


Volume 22, Number 12


, Pages 1142-1148

Type of Work:

Article | Post-print: After Peer Review


Summary Restless Legs Syndrome (RLS), first chronicled by Willis in 1672 and described in more detail by Ekbom in 1945 [1], is a prevalent sensorimotor neurological disorder (5–10% in the population) with a circadian predilection for the evening and night. Characteristic clinical features also include a compelling urge to move during periods of rest, relief with movement, involuntary movements in sleep (viz., periodic leg movements of sleep), and fragmented sleep [2,3]. While the pathophysiology of RLS is unknown, dopaminergic neurotransmission and deficits in iron availability modulate expressivity [1,4–9]. GWAS have identified a polymorphism in an intronic region of the BTBD9 gene on chromosome 6 that confers substantial risk for RLS [2,3,10–12]. Here, we report that loss of the Drosophila homolog CG1826 (dBTBD9) appreciably disrupts sleep with concomitant increases in waking and motor activity. We further show that BTBD9 regulates brain dopamine levels in flies and controls iron homeostasis through the iron regulatory protein-2 (IRP2) in human cell lines. To our knowledge, this represents the first reverse genetic analyses of a “novel” or heretofore poorly understood gene implicated in an exceedingly common and complex sleep disorder and the development of an RLS animal model that closely recapitulates all disease phenotypes.

Copyright information:

© 2012 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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