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Science 17 October 2003:
Vol. 302. no. 5644, pp. 439 - 442
DOI: 10.1126/science.1086593
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Reports

Requirement of Mammalian Timeless for Circadian Rhythmicity

Jessica W. Barnes,1* Shelley A. Tischkau,1,2* Jeffrey A. Barnes,1* Jennifer W. Mitchell,1 Penny W. Burgoon,1 Jason R. Hickok,1 Martha U. Gillette1{dagger}

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, where as a truncated isoform (mTIM-s) was constitutively expressed. mTIM-fl associated with the 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 negative-feedback arm of the mammalian molecular clockwork.

1 Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
2 Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.


* These authors contributed equally to this study.

{dagger} To whom correspondence should be addressed. E-mail: mgillett{at}uiuc.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)