Modeling feedback loops of the Mammalian circadian oscillator.

Modeling feedback loops of the Mammalian circadian oscillator. Research Abstract Details 

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Modeling feedback loops of the Mammalian circadian oscillator. Abstract Text:

Sabine Becker-Weimann,Jana Wolf,Hanspeter Herzel,Achim Kramer,

The suprachiasmatic nucleus governs daily variations of physiology and behavior in mammals. Within single neurons, interlocked transcriptional/translational feedback loops generate circadian rhythms on the molecular level. We present a mathematical model that reflects the essential features of the mammalian circadian oscillator to characterize the differential roles of negative and positive feedback loops. The oscillations that are obtained have a 24-h period and are robust toward parameter variations even when the positive feedback is replaced by a constantly expressed activator. This demonstrates the crucial role of the negative feedback for rhythm generation. Moreover, it explains the rhythmic phenotype of Rev-erbalpha-/- mutant mice, where a positive feedback is missing. The interplay of negative and positive feedback reveals a complex dynamics. In particular, the model explains the unexpected rescue of circadian oscillations in Per2Brdm1/Cry2-/- double-mutant mice (Per2Brdm1 single-mutant mice are arrhythmic). Here, a decrease of positive feedback strength associated with mutating the Per2 gene is compensated by the Cry2-/- mutation that simultaneously decreases the negative feedback strength. Finally, this model leads us to a testable prediction of a molecular and behavioral phenotype: circadian oscillations should be rescued when arrhythmic Per2Brdm1 mutant mice are crossed with Rev- erbalpha -/- mutant mice.

Modeling feedback loops of the Mammalian circadian oscillator. Publishing Authors By Initials

S Becker-Weimann,J Wolf,H Herzel,A Kramer,

For similar proteins: transcription factors research abstracts see: proteins: transcription factors research

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Modeling feedback loops of the Mammalian circadian oscillator. Journal Published:

PUBLICATION TYPE: Validation Studies

Journal: Biophysical journal

VOLUME: 87

Page Numbers: 3023-34

Journal Abbreviation: Biophys. J.

ISSN: 0006-3495

DAY: 3

MONTH: 09

YEAR: 2004

Modeling feedback loops of the Mammalian circadian oscillator. Information

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LANGUAGE: eng

NlmUniqueID: 370626

Modeling feedback loops of the Mammalian circadian oscillator. Keywords Mesh Terms:

KEYWORDS: Transcription Factors

MESH TERMS: physiology

Chemical & Substance for Abstract: Modeling feedback loops of the Mammalian circadian oscillator. Information

Substance Name: cryptochrome

Registry Number: 0

Grant and Affiliation Information for Modeling feedback loops of the Mammalian circadian oscillator.

AFFILIATION: Institute for Theoretical Biology, and Laboratory of Chronobiology--Institute of Medical Immunology (Charité), Humboldt-University Berlin, 10115 Berlin, Germany.

Country: United States

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MEDLINETA: Biophys J

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