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Tissue-specific function of Period3 in circadian rhythmicity - PubMed

Julie S Pendergast  1 , Kevin D Niswender, Shin Yamazaki

Tissue-specific function of Period3 in circadian rhythmicity

Julie S Pendergast et al. PLoS One. 2012.

Abstract

The mammalian circadian system is composed of multiple central and peripheral clocks that are temporally coordinated to synchronize physiology and behavior with environmental cycles. Mammals have three homologs of the circadian Period gene (Per1, 2, 3). While numerous studies have demonstrated that Per1 and Per2 are necessary for molecular timekeeping and light responsiveness in the master circadian clock in the suprachiasmatic nuclei (SCN), the function of Per3 has been elusive. In the current study, we investigated the role of Per3 in circadian timekeeping in central and peripheral oscillators by analyzing PER2::LUCIFERASE expression in tissues explanted from C57BL/6J wild-type and Per3⁻/⁻ mice. We observed shortening of the periods in some tissues from Per3⁻/⁻ mice compared to wild-types. Importantly, the periods were not altered in other tissues, including the SCN, in Per3⁻/⁻ mice. We also found that Per3-dependent shortening of endogenous periods resulted in advanced phases of those tissues, demonstrating that the in vitro phenotype is also present in vivo. Our data demonstrate that Per3 is important for endogenous timekeeping in specific tissues and those tissue-specific changes in endogenous periods result in internal misalignment of circadian clocks in Per3⁻/⁻ mice. Taken together, our studies demonstrate that Per3 is a key player in the mammalian circadian system.

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Conflict of interest statement

Competing Interests: Shin Yamazaki is an academic editor at PLoS ONE. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. Other authors declared that no competing interests exist.

Figures

Figure 1. Tissue-specific alterations of circadian periods in Per3−/− mice.

Bioluminescence was recorded from tissue explants prepared from male wild-type (black circles) and Per3−/− (red circles) mice maintained in 12L∶12D. The mean (± SD) periods were determined by fitting regression lines to the acrophases of the PER2::LUC rhythms. The sample size is shown (number of rhythmic tissues/number of tissues tested). WAT#: white adipose tissue surrounding the adrenal gland. *p<0.05; **p<0.01; ***p<0.001.

Figure 2. Altered circadian organization in Per3−/− mice.

Bioluminescence was recorded from tissue explants prepared from male wild-type (black circles) and Per3−/− (red circles) mice maintained in 12L∶12D. The mean phases (± SD) were determined from the peaks of PER2::LUC expression during the interval between 12 h and 36 h in culture and were plotted relative to the time of last lights-on, where 0 h is lights on and 12 h is lights off (black and white bar at top). The sample size is shown (number of rhythmic tissues/number of tissues tested). WAT#: white adipose tissue surrounding the adrenal gland. *p<0.05; **p<0.01; ***p<0.001.

Figure 3. Tissue-specific relationships between phase and period in wild-type and Per3−/− mice.

The phase of each sample was plotted relative to its endogenous period of PER2::LUC expression. All samples for which both phase and period could be analyzed are shown. Wild-type (black circles) and Per3−/− (red circles) samples are plotted on the same graph for each tissue. WAT#: white adipose tissue surrounding the adrenal gland.

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