Differential Effects of Light and Feeding on Circadian Organization of Peripheral Clocks in a Forebrain Bmal1 Mutant

作者：Izumo Mariko; Pejchal Martina; Schook Andrew C; Lange Ryan P; Walisser Jacqueline A; Sato Takashi R; Wang Xiaozhong; Bradfield Christopher A; Takahashi Joseph S^*

来源：eLife, 2014, 3: e04617.

DOI：10.7554/eLife.04617

• circadian rhythms
• Bmal1
• Cre/loxP
• suprachiasmatic nucleus
• peripheral clocks
• light entrainment
• food entrainment

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 %26gt;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 the internal temporal order of robust circadian programs in peripheral clocks; thus, individual peripheral clocks are affected differently by light and feeding in the absence of a functional oscillator in the forebrain.

• 出版日期2014-12-19
• 单位西北大学