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Circadian clock gene Bmal1 is not essential; functional replacement with its paralog, Bmal2
Shuqun Shi1, Akiko Hida, Owen P McGuinness
1Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
Current Biology : CB
|February 16, 2010
Summary
Brain and muscle ARNT-like 1 (Bmal1) and its paralog Bmal2 are functionally redundant circadian clock genes. Bmal1 knockout mice show rescued phenotypes when Bmal2 is expressed, suggesting Bmal2
Area of Science:
- Circadian biology
- Molecular genetics
- Mammalian physiology
Background:
- Most central circadian clock genes in mice exist as paralog pairs.
- Bmal1 (Brain and muscle ARNT-like 1) is considered essential, as its single knockout causes arrhythmicity.
- Bmal2 was previously thought to have a minimal role in the circadian clock system.
Purpose of the Study:
- To investigate the functional redundancy and regulatory relationship between Bmal1 and Bmal2.
- To determine if Bmal2 plays a more significant role in circadian rhythmicity and metabolism than previously understood.
Main Methods:
- Constitutive expression of Bmal2 in Bmal1-knockout mice.
- Assessment of circadian locomotor activity and metabolic parameters.
- Analysis of gene expression data from previous studies.
Main Results:
- Constitutive expression of Bmal2 rescued the arrhythmicity and metabolic phenotypes in Bmal1-knockout mice.
- Rescued phenotypes included restored rhythmic locomotor activity, normalized metabolism, reduced body weight, and mitigated fat deposition.
- Previous findings indicate Bmal1 knockout downregulates Bmal2 expression.
Conclusions:
- Bmal1 and Bmal2 function as a redundant circadian paralog pair.
- Bmal2's role is more significant than previously appreciated.
- Bmal1 regulates Bmal2 expression, implying a Bmal1 knockout effectively creates a double knockout of both genes.
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