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Elife. 2014 Dec 19;3. doi: 10.7554/eLife.04617.

Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant.

Author information

1
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States.
2
Department of Neurobiology, Northwestern University, Evanston, United States.
3
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, United States.
4
Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.
5
Department of Molecular Biosciences, Northwestern University, Evanston, United States.

Abstract

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.

KEYWORDS:

Arntl; Bmal1; Cre/loxP; Mop3; circadian rhythms; light entrainment; mouse; neuroscience; peripheral clocks; suprachiasmatic nucleus

PMID:
25525750
PMCID:
PMC4298698
DOI:
10.7554/eLife.04617
[Indexed for MEDLINE]
Free PMC Article

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