フォワード・ジェネティクスで同定した新規睡眠制御遺伝子による分子機構の解明

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Using the forward genetics approach, we established several mutant mice pedigree showing perturbed sleep/wake behavior. Sleepy2 mutant increase in the NREM sleep time, more pronounced during the dark phase. Notably, highly homologous family members of Sleepy2 gene family also showed aberrant sleep/wake behavior including the increase in sleep need.In order to understand the molecular and cellular mechanism of sleep homeostasis regulation, changes in gene signature can be examined by the next-generation sequencing. The study was designed at multiplexed level to examine both the effect of the gene mutation and sleep deprivation. Sleep need is a marker for the sleep homeostasis maintenance as it increases with prolonged wakefulness. The response following sleep deprivation can also be examined to assess normal maintenance of sleep/wakefulness. Several regions of the brain were selected and the samples from symmetrical hemisphere were processed for RNA- and ChIP-sequencing. This approach allows analysis of both transcriptomic and epigenetic changes affected by the various conditions applied by the study design.Based on the transcriptomics analysis, a brain region is narrowed down for more vigorous and scrutinized study for the changes in gene signature. An extensive data integration will be performed to map the interacting molecules and signal transduction pathway. This will supplement the currently available pathway database with sleep/wake regulation specific mechanism.