Open Close
Freeman, A., Pranski, E., Miller, R.D., Radmard, S., Bernhard, D., Jinnah, H.A., Betarbet, R., Rye, D.B., Sanyal, S. (2012). Sleep fragmentation and motor restlessness in a Drosophila model of restless legs syndrome.  Curr. Biol. 22(12): 1142--1148.
FlyBase ID
Publication Type
Research paper

Restless Legs Syndrome (RLS), first chronicled by Willis in 1672 and described in more detail by Ekbom in 1945, 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. Although the pathophysiology of RLS is unknown, dopaminergic neurotransmission and deficits in iron availability modulate expressivity. Genome-wide association studies have identified a polymorphism in an intronic region of the BTBD9 gene on chromosome 6 that confers substantial risk for RLS. 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 in human cell lines. To our knowledge, this represents the first reverse genetic analysis 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.

PubMed ID
PubMed Central ID
PMC3381864 (PMC) (EuropePMC)
Related Publication(s)

An emerging role for Cullin-3 mediated ubiquitination in sleep and circadian rhythm: Insights from Drosophila.
Freeman et al., 2013, Fly 7(1): 39--43 [FBrf0221493]

Neurological disorders: towards a mechanistic understanding of restless legs syndrome.
Shaw and Duntley, 2012, Curr. Biol. 22(12): R485--R486 [FBrf0218693]

Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Curr. Biol.
    Current Biology
    Publication Year
    Data From Reference
    Alleles (10)
    Genes (3)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (2)
    Transgenic Constructs (6)