Publication Date


Document Type

Doctoral Dissertation

Academic Program




First Thesis Advisor

David Weaver


Circadian Rhythms, Clock


Circadian rhythms are the outward manifestation of an internal timing system that measures time in 24-hr increments. The mammalian circadian system is hierarchical, with a pacemaker in the suprachiasmatic nucleus (SCN) synchronizing cell-autonomous oscillators in peripheral tissues. Much of what we know about rhythmicity in peripheral tissues comes from studies monitoring bioluminescence rhythms in PERIOD2::LUCIFERASE knock-in mice. A limitation with this model is that rhythmicity cannot be monitored in specific cells due to widespread reporter expression. To address this shortcoming, we generated a mouse that expresses luciferase from the Dbp locus only after Cre-mediated recombination. I validated this conditional mouse to provide a tool for monitoring circadian rhythms in a tissue/cell-specific manner. Crossing the conditional reporter mice with mice expressing Cre recombinase in various cell types allowed detection of rhythmic bioluminescence in the expected tissues, in vivo and ex vivo, as well as in slice cultures containing the SCN. The phase of bioluminescence rhythms from explants of mouse peripheral tissues indicated that DbpLuc/+ bioluminescence rhythms have an earlier phase than PER2::LUC/+ rhythms. Importantly, we confirmed that editing of the Dbp locus did not alter the period of circadian locomotor activity rhythms and did not alter liver Dbp RNA rhythms. Finally, the reporter mouse allows for monitoring rhythms in specific tissues in ambulatory mice. Thus, this mouse line is useful for studying circadian rhythms in a tissue/cell-type specific manner, which can be used to better monitor phase relationships between tissues at baseline and after environmental perturbations that disrupt circadian rhythms.



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