Phenotypic rescue of a peripheral clock genetic defect via SCN hierarchical dominance.
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 clock(c/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.
Pando
Matthew P
MP
Institute de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP, 1 rue Laurent Fries, 67404 Illkirch, Strasbourg, France.
Morse
David
D
Cermakian
Nicolas
N
Sassone-Corsi
Paolo
P
D000818:Animals; D001683:Biological Clocks / Q000235:genetics* / Q000502:physiology; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D005247:Feeding Behavior; D005347:Fibroblasts / Q000502:physiology / Q000637:transplantation; D015870:Gene Expression; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D056950:Period Circadian Proteins; D010641:Phenotype; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D014157:Transcription Factors
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors