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

Mariko Izumo | Martina Pejchal | Andrew C Schook | Ryan P Lange | Jacqueline A Walisser | Takashi R Sato | Xiaozhong Wang | Christopher A Bradfield | Joseph S Takahashi
eLife | 2014

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.

Pubmed ID: 25525750

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: U01 MH61915
  • Agency: Howard Hughes Medical Institute, United States
    Id: H0690101
  • Agency: NIMH NIH HHS, United States
    Id: P50 MH074924
  • Agency: NIEHS NIH HHS, United States
    Id: R01 ES005703
  • Agency: NINDS NIH HHS, United States
    Id: 1F30NS056551-01

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