TY - JOUR
T1 - Chimera analysis of the Clock mutation in mice shows that complex cellular integration determines circadian behavior
AU - Low-Zeddies, Sharon S.
AU - Takahashi, Joseph S.
N1 - Funding Information:
We are grateful to Dr. P. Iannaccone and his laboratory for instruction in embryo aggregation techniques; Dr. D. Ferster for data analysis software support; Drs. A. Bejsovec, K. Herrup, P. DeCoursey, W. Schwartz, F. Davis, E. Herzog, M. Lehman, and members of the Takahashi laboratory for useful discussions and advice during the course of this experiment; Drs. M. Hurd and M. Ralph for their X-gal staining protocol; and the excellent services of the animal caretakers in the Center for Experimental Animal Resources, Northwestern University. Thanks to David Zeddies for comments on the manuscript, and for encouragement. Supported by the NSF Center for Biological Timing, an Unrestricted Grant in Neuroscience from the Bristol-Myers Squibb Foundation and the National Institute of Mental Health. J. S. T. is an Investigator in the Howard Hughes Medical Institute.
PY - 2001/4/6
Y1 - 2001/4/6
N2 - The Clock mutation lengthens periodicity and reduces amplitude of circadian rhythms in mice. The effects of Clock are cell intrinsic and can be observed at the level of single neurons in the suprachiasmatic nucleus. To address how cells of contrasting genotype functionally interact in vivo to control circadian behavior, we have analyzed a series of Clock mutant mouse aggregation chimeras. Circadian behavior in Clock/Clock ↔ wild-type chimeric individuals was determined by the proportion of mutant versus normal cells. Significantly, a number of intermediate phenotypes, including Clock/+ phenocopies and novel combinations of the parental behavioral characteristics, were seen in balanced chimeras. Multivariate statistical techniques were used to quantitatively analyze relationships among circadian period, amplitude, and suprachiasmatic nucleus composition. Together, our results demonstrate that complex integration of cellular phenotypes determines the generation and expression of coherent circadian rhythms at the organismal level.
AB - The Clock mutation lengthens periodicity and reduces amplitude of circadian rhythms in mice. The effects of Clock are cell intrinsic and can be observed at the level of single neurons in the suprachiasmatic nucleus. To address how cells of contrasting genotype functionally interact in vivo to control circadian behavior, we have analyzed a series of Clock mutant mouse aggregation chimeras. Circadian behavior in Clock/Clock ↔ wild-type chimeric individuals was determined by the proportion of mutant versus normal cells. Significantly, a number of intermediate phenotypes, including Clock/+ phenocopies and novel combinations of the parental behavioral characteristics, were seen in balanced chimeras. Multivariate statistical techniques were used to quantitatively analyze relationships among circadian period, amplitude, and suprachiasmatic nucleus composition. Together, our results demonstrate that complex integration of cellular phenotypes determines the generation and expression of coherent circadian rhythms at the organismal level.
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U2 - 10.1016/S0092-8674(01)00294-X
DO - 10.1016/S0092-8674(01)00294-X
M3 - Article
C2 - 11301000
AN - SCOPUS:0035815289
SN - 0092-8674
VL - 105
SP - 25
EP - 42
JO - Cell
JF - Cell
IS - 1
ER -