Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant
| Autor: | Andrew C. Schook, Joseph S. Takahashi, Martina Pejchal, Jacqueline A. Walisser, Takashi R Sato, Christopher A. Bradfield, Ryan P Lange, Xiaozhong Wang, Mariko Izumo |
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| Rok vydání: | 2014 |
| Předmět: |
endocrine system
Light QH301-705.5 Science Biology General Biochemistry Genetics and Molecular Biology peripheral clocks Mice Biological Clocks Cre/loxP Animals Circadian rhythm Biology (General) mouse Mice Knockout General Immunology and Microbiology ARNTL Transcription Factors Suprachiasmatic nucleus General Neuroscience suprachiasmatic nucleus General Medicine Anatomy Feeding Behavior Cell biology Peripheral Circadian Rhythm ARNTL Bmal1 peripheral clock nervous system circadian rhythms light entrainment Knockout mouse Forebrain Mutation Medicine Mop3 Cre-Lox recombination sense organs Arntl Research Article Neuroscience |
| Zdroj: | eLife eLife, Vol 3 (2014) |
| ISSN: | 2050-084X |
| Popis: | In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus (SCN) to circadian behavior and the organization of peripheral clocks, we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines. The forebrain knockout mice showed >90% deletion of BMAL1 in the SCN and exhibited an immediate and complete loss of circadian behavior in constant conditions. Circadian rhythms in peripheral tissues persisted but became desynchronized and damped in constant darkness. The loss of synchrony was rescued by light/dark cycles and partially by restricted feeding (only in the liver and kidney but not in the other tissues) in a distinct manner. These results suggest that the forebrain/SCN is essential for internal temporal order of robust circadian programs in peripheral clocks, and that individual peripheral clocks are affected differently by light and feeding in the absence of a functional oscillator in the forebrain. DOI: http://dx.doi.org/10.7554/eLife.04617.001 eLife digest Jet lag is a common experience when flying long distance. This disorientating phenomenon occurs when our internal ‘body clock’ remains set to the time zone where the plane departed and fails to reset to the new local time. Our internal clock actually consists of a series of clocks—each of which is based upon groups of genes that are switched on and off at different times of the day and night. There is a master clock in our brain and a series of peripheral clocks in our other organs and tissues. The master clock is thought to coordinate the peripheral clocks, which in turn control the fluctuating activity of a specific organ in response to the time of day. To further investigate the master clock, a typical approach has been made to disable it by deleting the genes for its components. But some of these deletions can cause abnormalities in mice and some are lethal. To get around these problems, Izumo, Pejchal et al. have devised a way to delete a molecular component of the master clock only in the mouse's brain. Izumo, Pejchal et al. used this approach to specifically disable the mouse's master clock and, unlike mice that completely lack the Bmal1 gene, mice with the brain-specific deletion were as healthy and lived as long as normal mice. A molecular probe was used to monitor the peripheral clocks in different organs and tissues of these mutant mice, and revealed that, without a working master clock, the peripheral clocks were no longer synchronized. Izumo, Pejchal et al. found that the lost synchrony could be partially restored by training the mice to adapt to cycles of light and dark and feeding schedules. Following on from the work of Izumo, Pejchal et al., one of the next challenges is to understand how the master clock communicates with the peripheral clocks in different organs and tissues around the body. DOI: http://dx.doi.org/10.7554/eLife.04617.002 |
| Databáze: | OpenAIRE |
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