A mammalian ortholog of Drosophila timeless, highly expressed in SCN and retina, forms a complex with mPER1.
BACKGROUND
It is now becoming clear that the circadian rhythm of behaviours and hormones arises from a rhythm at the level of gene expression, and that mammals and Drosophila essentially use homologous genes as molecular gears in the control of circadian oscillation. In Drosophila, the period and timeless genes form a functional unit of the clock and its autoregulatory feedback loop for circadian rhythm. However, in mammals, the counterpart of timeless has not been found.


RESULTS
We have isolated a mammalian homologue of timeless, mTim, from the mouse brain. mTim is highly expressed, with a weak or absent rhythm in the suprachiasmatic nucleus, the mammalian circadian centre. In the retina, mTim mRNA was found to be expressed with a circadian rhythm, and a particularly robust cycle was observed in the presence of light/dark cycles. We demonstrated that mTIM physically associates with mPER1 in vitro and in the nuclei of cultured COS7 cells.


CONCLUSIONS
We have reported the isolation of the mouse timeless cDNA, the expression of the mTim mRNA and an interaction of mTIM with mPER1. These results indicate that the autoregulatory feedback mechanism of circadian oscillation of the period gene may also be conserved in mammals.
Takumi
T
T
Department of Anatomy and Brain Science, Kobe University School of Medicine, Kobe 650-0017, Japan; CREST, Japan Science and Technology Corporation, Japan.
Nagamine
Y
Y
Miyake
S
S
Matsubara
C
C
Taguchi
K
K
Takekida
S
S
Sakakida
Y
Y
Nishikawa
K
K
Kishimoto
T
T
Niwa
S
S
Okumura
K
K
Okamura
H
H
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D056950:Period Circadian Proteins; D012160:Retina / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D013997:Time Factors
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; C096445:tim protein, Drosophila