Analysis of core circadian feedback loop in suprachiasmatic nucleus of mCry1-luc transgenic reporter mouse
| Autor: | Nicola J. Smyllie, Michael H. Hastings, Johanna E. Chesham, Marco Brancaccio, John S. O’Neill, Elizabeth S. Maywood, Hugues Dardente, Jean-Michel Fustin, Gemma F. Codner, David G. Hazlerigg, Lesley F Drynan, Mathew D. Edwards |
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| Přispěvatelé: | Neurobiology Division, Laboratory of Molecular Biology, Medical Research Council, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Institute of Biological and Environmental Sciences, University of Aberdeen, Cell Biology Division, Mary Lyon Centre, Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Hastings, Michael H |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
rythme circadien
medicine.medical_specialty endocrine system animal structures Period (gene) [SDV]Life Sciences [q-bio] Vasoactive intestinal peptide Mice Transgenic souris Biology vpac2 03 medical and health sciences Transactivation Mice 0302 clinical medicine Cryptochrome Internal medicine period gene medicine Cyclic AMP Animals Luciferase Circadian rhythm afterhours Luciferases adenylate cyclase gene expression 030304 developmental biology DNA Primers Feedback Physiological 0303 health sciences Multidisciplinary Suprachiasmatic nucleus Period Circadian Proteins Biological Sciences Cell biology Circadian Rhythm Cryptochromes Mice Inbred C57BL Endocrinology animal transgénique Suprachiasmatic Nucleus sense organs noyau suprachiasmatique 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2013, 110 (23), pp.9547-9552. ⟨10.1073/pnas.1220894110⟩ Proceedings of the National Academy of Sciences of the United States of America 23 (110), 9547-9552. (2013) |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.1220894110⟩ |
| Popis: | The suprachiasmatic nucleus (SCN) coordinates circadian rhythms that adapt the individual to solar time. SCN pacemaking revolves around feedback loops in which expression of Period ( Per ) and Cryptochrome ( Cry ) genes is periodically suppressed by their protein products. Specifically, PER/CRY complexes act at E-box sequences in Per and Cry to inhibit their transactivation by CLOCK/BMAL1 heterodimers. To function effectively, these closed intracellular loops need to be synchronized between SCN cells and to the light/dark cycle. For Per expression, this is mediated by neuropeptidergic and glutamatergic extracellular cues acting via cAMP/calcium-responsive elements (CREs) in Per genes. Cry genes, however, carry no CREs, and how CRY-dependent SCN pacemaking is synchronized remains unclear. Furthermore, whereas reporter lines are available to explore Per circadian expression in real time, no Cry equivalent exists. We therefore created a mouse, B6.Cg-Tg(Cry1-luc)01Ld, carrying a transgene ( mCry1-luc ) consisting of mCry1 elements containing an E-box and E′-box driving firefly luciferase. mCry1-luc organotypic SCN slices exhibited stable circadian bioluminescence rhythms with appropriate phase, period, profile, and spatial organization. In SCN lacking vasoactive intestinal peptide or its receptor, mCry1 expression was damped and desynchronized between cells. Despite the absence of CREs, mCry1-luc expression was nevertheless (indirectly) sensitive to manipulation of cAMP-dependent signaling. In mPer1/2 -null SCN, mCry1-luc bioluminescence was arrhythmic and no longer suppressed by elevation of cAMP. Finally, an SCN graft procedure showed that PER-independent as well as PER-dependent mechanisms could sustain circadian expression of mCry1 . The mCry1-luc mouse therefore reports circadian mCry1 expression and its interactions with vasoactive intestinal peptide, cAMP, and PER at the heart of the SCN pacemaker. |
| Databáze: | OpenAIRE |
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