Department of Neurobiology; Graduate School of Biomedical Sciences, Program in Neuroscience; Department of Molecular, Cell and Cancer Biology; Department of Biochemistry and Molecular Pharmacology; NeuroNexus Institute; Weaver Lab
Albumins; Animals; Circadian Rhythm; Genes, Reporter; Luciferases; Mice; Photoperiod; Suprachiasmatic Nucleus
Cellular and Molecular Physiology | Neuroscience and Neurobiology
Circadian rhythms are endogenously generated physiological and molecular rhythms with a cycle length of about 24 h. Bioluminescent reporters have been exceptionally useful for studying circadian rhythms in numerous species. Here, we report development of a reporter mouse generated by modification of a widely expressed and highly rhythmic gene encoding D-site albumin promoter binding protein (Dbp). In this line of mice, firefly luciferase is expressed from the Dbp locus in a Cre recombinase-dependent manner, allowing assessment of bioluminescence rhythms in specific cellular populations. A mouse line in which luciferase expression was Cre-independent was also generated. The Dbp reporter alleles do not alter Dbp gene expression rhythms in liver or circadian locomotor activity rhythms. In vivo and ex vivo studies show the utility of the reporter alleles for monitoring rhythmicity. Our studies reveal cell-type-specific characteristics of rhythms among neuronal populations within the suprachiasmatic nuclei ex vivo. In vivo studies show Dbp-driven bioluminescence rhythms in the liver of Albumin-Cre;DbpKI/+ "liver reporter" mice. After a shift of the lighting schedule, locomotor activity achieved the proper phase relationship with the new lighting cycle more rapidly than hepatic bioluminescence did. As previously shown, restricting food access to the daytime altered the phase of hepatic rhythmicity. Our model allowed assessment of the rate of recovery from misalignment once animals were provided with food ad libitum. These studies confirm the previously demonstrated circadian misalignment following environmental perturbations and reveal the utility of this model for minimally invasive, longitudinal monitoring of rhythmicity from specific mouse tissues.
circadian rhythms, bioluminescence, luciferase, misalignment, Dbp, albumin D-element binding protein, In Vivo Imaging System, LumiCycle In Vivo, reporter mouse, peripheral oscillators
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© 2022 SAGE Publications. Accepted manuscript posted as allowed by the publisher's author archiving and sharing policy at https://uk.sagepub.com/en-gb/eur/journal-author-archiving-policies-and-re-use. Reuse is restricted to non-commercial and no derivative uses.
DOI of Published Version
Smith CB, van der Vinne V, McCartney E, Stowie AC, Leise TL, Martin-Burgos B, Molyneux PC, Garbutt LA, Brodsky MH, Davidson AJ, Harrington ME, Dallmann R, Weaver DR. Cell-Type-Specific Circadian Bioluminescence Rhythms in Dbp Reporter Mice. J Biol Rhythms. 2022 Feb;37(1):53-77. doi: 10.1177/07487304211069452. Epub 2022 Jan 13. PMID: 35023384; PMCID: PMC9245534. https://doi.org/10.1177/07487304211069452
Journal of biological rhythms
Smith CB, van der Vinne V, McCartney E, Stowie AC, Leise TL, Martin-Burgos B, Molyneux PC, Garbutt LA, Brodsky MH, Davidson AJ, Harrington ME, Dallmann R, Weaver DR. (2022). Cell-Type-Specific Circadian Bioluminescence Rhythms in Dbp Reporter Mice. Neurobiology Publications. https://doi.org/10.1177/07487304211069452. Retrieved from https://escholarship.umassmed.edu/neurobiology_pp/263