| Budget Amount *help |
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2006: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2005: ¥9,300,000 (Direct Cost: ¥9,300,000)
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| Research Abstract |
Sleep is a physiological brain function observed in broad animal species including fruit fly, Drosophila melanogaster. Recent progress in molecular analysis of sleep and arousal regulations in Drosophila validated the homology between insect and mammals. We identified a spontaneous Drosophila mutant with a hyperactive, sleepless activity pattern and named it fumin. We then identified this phenotype was caused by the mutation in the dopamine transporter gene using forward genetics approach. A fragment of transposon was inserted into the intron, which deteriorates splicing and the resulting mRNA gives only a truncated protein presumably with no function. The dopamine transporter affected is found in mammalian brain and it is regarded as a target of psychostimulants such as amphetamine and cocaine. This result suggested that the arousal mechanisms of Drosophila and mammals share common molecules and genes. We then analyzed the phenotypes of fumin more in detail. Two major findings were established during this project.
First, the longetivity of fumin is equivalent to the wild type control despite they show 3 to 4 fold increase in total activity and one third to one fourth decrease in total sleep amount. However, when fumin mutants were fed with high calorie diet, they gradually increase their activities and they show shorter life span than the wild type. This result suggested that there is a minimal requirement period of sleep in Drosophila.
Second, we applied fumin mutant caffeine, which is an arousal inducing agent commonly used by human. Surprisingly, fumin was more sensitive to caffeine than wild type, and they show dramatically increased activity and decreased sleep. Moreover, caffeine was more toxic to fumin, and with the dose which is not toxic to wild type, fumin mutant die quickly. This result also suggested that there is a minimal requirement of sleep in Drosophila.
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