Physiology

Restless Flies Show Their Legs

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Science  13 Jul 2012:
Vol. 337, Issue 6091, pp. 135
DOI: 10.1126/science.337.6091.135-a

Your leg may not seem to have much in common with that of a fly; however, it may be more than you think. Freeman et al. show that a relatively common human neurological disorder called restless legs syndrome, characterized by a strong urge to move one's legs and “fragmented” sleep, can be modeled in the fruit fly Drosophila melanogaster. A polymorphism in the gene BTBD9 confers approximately 50% of the population-attributable risk in the human disorder. Deletion of the homolog in Drosophila, dBTBD9, recapitulated features of this condition, such as altered rest activity cycles, disrupted sleep, and hyperlocomotion. Knockdown of dBTBD9 in a specific set of dopaminergic neurons also resulted in fragmented sleep. Also similar to the human disorder, aberrant dopamine levels were observed in the dBTBD9 mutant fly brain. Treatment of mutant flies with a dopamine agonist improved sleep patterns. In human cells, iron homeostasis was controlled by BTBD9. These findings support prior studies suggesting a role for dopamine regulation and iron metabolism in restless legs syndrome. Furthermore, the fly may serve as a useful model for understanding this disorder.

Curr. Biol. 22, 1142 (2012).

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