Requirement of Mammalian Timeless for Circadian Rhythmicity

J. W. Barnes
2003 Science  
Despite a central circadian role in Drosophila for the transcriptional regulator Timeless (dTim), the relevance of mammalian Timeless (mTim) remains equivocal. Conditional knockdown of mTim protein expression in the rat suprachiasmatic nucleus (SCN) disrupted SCN neuronal activity rhythms, and altered levels of known core clock elements. Full-length mTim protein (mTIM-fl) exhibited a 24-hour oscillation, whereas a truncated isoform (mTIM-s) was constitutively expressed. mTIM-fl associated with
more » ... he mammalian clock Period proteins (mPERs) in oscillating SCN cells. These data suggest that mTim is required for rhythmicity and is a functional homolog of dTim on the negativefeedback arm of the mammalian molecular clockwork.
doi:10.1126/science.1086593 pmid:14564007 fatcat:sd2hzgtnfrfsfkqyz3tqzqp634