| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
Almost all organisms have their circadian rhythms with periods of approximately 24 hours. Circadian rhythms are generated in pacemaker cells and are entrained by environmental cues, such as light and temperature. The output of a circadian oscillation appears as locomotive activity, hormonal secretion, the steep-wake cycle, and many physiological functions. Recent molecular dissection has revealed that the feedback loop is the basic concept of the circadian oscillator, conserved across the species from Neurospora and Drosophila to mice. We have isolated a mammalian homologue of clock genes from the mouse brain.
1) To clarify the in vivo function of mammalian clock genes, we introduced the mammalian Per genes under Drosophila tim promoter into the null mutant per0 and have found in vivo rescue in some colonies.
2) We isolated human hPer3 cDNA and genome and found, compared with mPer3, VNTR (variable number of tandem repeats), SVs (splicing variants) and SNPs (single nucleotide polymorphisms).
3) We isolated a new zinc-finger type of transcription factor (Lot1) by differential display method. The Lot1 mRNA is highly expressed in SCN, the mammalian circadian center, during P1 to P10.
4) We showed expression of mPER2 and mPER3 protein in a circadian manner by serum shock to cultured N1H3T3 cells, but no rhythmic expression of TIM proteins.
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