Cell
Volume 110, Issue 1, 12 July 2002, Pages 107-117
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Article
Phenotypic Rescue of a Peripheral Clock Genetic Defect via SCN Hierarchical Dominance

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Abstract

The mammalian circadian system contains both central and peripheral oscillators. To understand the communication pathways between them, we have studied the rhythmic behavior of mouse embryo fibroblasts (MEFs) surgically implanted in mice of different genotypes. MEFs from Per1−/− mice have a much shorter period in culture than do tissues in the intact animal. When implanted back into mice, however, the Per1−/− MEF take on the rhythmic characteristics of the host. A functioning clock is required for oscillations in the target tissues, as arrhythmic clockc/c MEFs remain arrhythmic in implants. These results demonstrate that SCN hierarchical dominance can compensate for severe intrinsic genetic defects in peripheral clocks, but cannot induce rhythmicity in clock-defective tissues.

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3

Present address: ExonHit Therapeutics, 217 Perry Parkway, Building 5, Gaithersburg, Maryland 20877.

4

On leave from the Département des Sciences Biologiques, Université de Montréal, 4101 Sherbrooke est, Montréal (QC) H1X 2B2, Canada.

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Present address: Douglas Hospital Research Center, McGill University, 6875 LaSalle Blvd, Montreal (QC) H4H 1R3, Canada.