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2016 ; 6
(ä): 32769
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Rigid Cooperation of Per1 and Per2 proteins
#MMPMID27609640
Tamiya H
; Ogawa S
; Ouchi Y
; Akishita M
Sci Rep
2016[Sep]; 6
(ä): 32769
PMID27609640
show ga
Period circadian clock (Per) genes Per1 and Per2 have essential roles in
circadian oscillation. In this study, we identified a new role of Per1-Per2
cooperation, and its mechanism, using our new experimental methods. Under
constant light conditions, the period length of Per1 and Per2 knockout mice
depended on the copy number ratio of Per1:Per2. We then established a
light-emitting diode-based lighting system that can generate any pattern of light
intensity. Under gradually changing light in the absence of phase shift with
different periods, both Per1((-/-)) and Per2((-/-)) mice were entrained to a
broader range of period length than wild-type mice. To analyse Per1-Per2
cooperative roles at the cell culture level, we established a Per2
knockout-rescue system, which can detect period shortening in a familial advanced
sleep phase syndrome (FASPS) mutant. Upon introduction of the Per1 coding region
in this system, we saw period shortening. In conclusion, short period-associated
protein Per1 and long period-associated Per2 cooperated to rigidly confine the
circadian period to "circa" 24-h. These results suggest that the rigid circadian
rhythm maintained through the cooperation of Per1-Per2 could negatively impact
modern society, in which the use of artificial lighting is ubiquitous, and result
in circadian disorders, including delirium.