Chimera analysis of the Clock mutation in mice shows that complex cellular integration determines circadian behavior

Sharon S. Low-Zeddies, Joseph S. Takahashi

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)25-42
Number of pages18
JournalCell
Volume105
Issue number1
DOIs
StatePublished - Apr 6 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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