期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 35, 页码 14218-14223出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1206213109
关键词
food anticipatory activity; restricted feeding; suprachiasmatic nuclei; knockout; C57BL/6J
资金
- National Science Foundation [IOS-1146908]
- National Mouse Metabolic Phenotyping Centers MICROMouse Program [U24DK076169]
- Tennessee Valley Healthcare System
- National Institutes of Health [DK085712]
- Diabetes Research and Training Center [DK20593]
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [1146908] Funding Source: National Science Foundation
Daily rhythmic processes are coordinated by circadian clocks, which are present in numerous central and peripheral tissues. In mammals, two circadian clocks, the food-entrainable oscillator (FEO) and methamphetamine-sensitive circadian oscillator (MASCO), are black box mysteries because their anatomical loci are unknown and their outputs are not expressed under normal physiological conditions. In the current study, the investigation of the timekeeping mechanisms of the FEO and MASCO in mice with disruption of all three paralogs of the canonical clock gene, Period, revealed unique and convergent findings. We found that both the MASCO and FEO in Per1(-/-)/Per2(-/-)/Per3(-/-) mice are circadian oscillators with unusually short (similar to 21 h) periods. These data demonstrate that the canonical Period genes are involved in period determination in the FEO and MASCO, and computational modeling supports the hypothesis that the FEO and MASCO use the same timekeeping mechanism or are the same circadian oscillator. Finally, these studies identify Per1(-/-)/Per2(-/-)/Per3(-/-) mice as a unique tool critical to the search for the elusive anatomical location(s) of the FEO and MASCO.
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