Sleep and Circadian Rhythms in Fragile X Mutant Drosophila

Dr. Ravi Allada at Northwestern University investigated sleep behaviors in Fragile X fruit flies. These flies are useful for several important reasons; not only do they have a good cognitive phenotype, they also have a clear disturbance of circadian rhythms. This is an important model for human hyperactivity and sleep disorders.

Ravi Allada, MD, at Northwestern University, FRAXA research grant
$80,000 Grant
Ravi Allada, MD
Principal Investigator

Chunghun Lim, PhD
FRAXA Postdoctoral Fellow

Elaine Merrill Smith, PhD
FRAXA Postdoctoral Fellow

Northwestern University
2007-2008 FRAXA Research Grant
$80,000 over 2 Years

Sleep and Circadian Rhythms in Fragile X Mutant Drosophila

by Elaine Merrill Smith, 4/1/2007

People with Fragile X mental retardation often exhibit a range of sleep disruptions in addition to the developmental, cognitive and behavioral deficits associated with this disorder. Specifically, patients are reported to have diminished overall levels of sleep and problems with sleep patterns and quality. The fruit fly Drosophila melanogaster has a copy of the gene responsible for Fragile X mental retardation that is very similar to its human counterpart.

Notably, flies lacking dfmr exhibit a variety of altered behaviors consistent with the symptoms of Fragile X. Like others, I have characterized the disruption of circadian rhythms in dfmr mutant Drosophila. Circadian rhythms control the daily timing of physiology and behavior in organisms from bacteria to humans. In addition to very weak circadian rhythms, I have demonstrated that flies mutant for dfmr also have decreased levels of sleep and score poorly on measures of sleep quality, just as is observed in human Fragile X cases.

This grant seeks to follow two lines of inquiry. The first is to test whether the altered behaviors in dfmr mutants can be restored with a normal copy of the dfmr gene introduced only during adulthood, or whether function of this gene is also required during development. Determining the timing of dfmr function will allow a better understanding of its acute role in sleep and circadian rhythms, and can direct treatments to the stage most likely to avert the disorder. Secondly, I will continue to investigate the link between dfmr and genes with known function in order to shed light on the normal activity of dfmr with regard to sleep and rhythms. These findings may yield novel targets for therapeutic development and provide insight to how Fragile X symptoms arise when FMR function is disrupted.

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