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The Journal of Neuroscience, 1999, 0:RC11:1-7
RAPID COMMUNICATION
Differential Regulation of mPER1 and mTIM Proteins in the Mouse
Suprachiasmatic Nuclei: New Insights into a Core Clock Mechanism
Michael H.
Hastings1,
Manuel D.
Field1,
Elizabeth
S.
Maywood1,
David R.
Weaver2, and
Steven M.
Reppert2
1 Department of Anatomy, University of Cambridge,
Cambridge CB2 3DY, United Kingdom, and 2 Laboratory of
Developmental Chronobiology, Pediatric Service, Massachusetts General
Hospital and Harvard Medical School, Boston Massachusetts 02214
Recent discoveries have identified a framework for the core
circadian clock mechanism in mammals. Development of this framework has
been based entirely on the expression patterns of so-called "clock
genes" in the suprachiasmatic nuclei (SCN), the principal clock of
mammals. We now provide data concerning the protein expression patterns
of two of these genes, mPer1 and mTim.
Our studies show that mPER1 and mTIM are nuclear antigens expressed in
the SCN and extensively throughout the forebrain. Expression of mPER1 in the SCN was rhythmic under entrained conditions and with clear circadian cycling under free-running conditions. Expression of mPER1
elsewhere in the mouse forebrain was not rhythmic. In contrast to
mPER1, mTIM expression in the SCN did not vary with time in mice housed
in either a light/dark cycle or in constant dim red light. The phase
relationship between mPer1 RNA and mPER1 cycles in the
SCN is consistent with a negative feedback model of the mammalian
clock. The invariant nature of nuclear mTIM in the SCN suggests that
its participation in negative feedback occurs only after mPER1 has
entered the nucleus, and that the abundance of mTIM is not regulated by
the circadian clock or the light/dark cycle.
Key words:
circadian clock; suprachiasmatic nucleus; clock gene; mPER; mTIM; negative feedback; period; timeless
Copyright © 1999 Society for Neuroscience 0270-6474/99/$05.00/0
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