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Oscillating perceptions: the ups and downs of the CLOCK protein in the mouse circadian system
1Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. debruyne@mail.med.upenn.edu
Abstract:
A functional mouse CLOCK protein has long been thought to be essential for mammalian circadian clockwork function, based mainly on studies of mice bearing a dominant negative, antimorphic mutation in the Clock gene. However, new discoveries using recently developed Clock-null mutant mice have shaken up this view. In this review, I discuss how this recent work impacts and alters the previous view of the role of CLOCK in the mouse circadian clockwork.
Insights
New studies on Clock-null mutant mice challenge the long-held view that a functional CLOCK protein is essential for the mammalian circadian clock. This review examines how these findings alter our understanding of CLOCK's role.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- The CLOCK protein has been considered crucial for mammalian circadian rhythms.
- This belief was primarily based on studies using mice with a dominant-negative mutation in the Clock gene.
Purpose of the Study:
- To review recent findings on Clock-null mutant mice.
- To re-evaluate the established role of CLOCK in the mouse circadian clockwork.
Main Methods:
- Analysis of studies involving Clock-null mutant mice.
- Comparison of new data with previous findings from antimorphic Clock mutation models.
Main Results:
- Recent research using Clock-null mutant mice presents a revised perspective on CLOCK protein function.
- The essentiality of CLOCK for circadian clockwork is being questioned.
Conclusions:
- New discoveries necessitate a re-evaluation of the CLOCK protein's role in mammalian circadian rhythms.
- The impact of Clock-null mutations offers a clearer understanding of circadian clock mechanisms.
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