Circadian behavior of mice deficient in PER1/PML or PER2/PML

Authors

Takao Miki Department of Biochemistry and Molecular Biology, Medical School, University of Texas Health Science Center-Houston, Houston, TX and Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Kyoto
Misty Chen-Goodspeed Department of Biochemistry and Molecular Biology, Medical School, University of Texas Health Science Center-Houston, Houston, TX
Zhaoyang Zhao Department of Biochemistry and Molecular Biology, Medical School, University of Texas Health Science Center-Houston, Houston, TX
Cheng Chi Lee Department of Biochemistry and Molecular Biology, Medical School, University of Texas Health Science Center-Houston, Houston, TX

DOI:

Keywords:

Circadian rhythm, Mouse model, Actogram, Phase shift, Period

Abstract

Background: Our recent studies demonstrate that the murine homolog of the human tumor suppressor promyelocytic leukemia (PML) regulates circadian behavior of mice. To further gather insight into PML’s contribution to circadian behavior, we generated two strains of mice deficient in one of the two period (Per) genes and the PML gene, with Per1^−/−/Pml^−/− and Per2^−/−/Pml^−/− genotypes.

Results: Here we report the circadian behavior of these mice based on wheel-running behavioral analysis. In a free-running environment, the Per1^−/−/Pml^−/− mice maintained circadian rhythm but displayed a significantly shorter period of 22.2 h. In addition, these mice displayed significantly enhanced phase response to a light pulse given at zeitgeber time (ZT) 14 and 22. The Per2^−/−/Pml^−/− mice lose persistent rhythm when in a free-running environment, as also the case forPer2^−/− mice. A transient post-light pulse rhythm seen in the arrhythmic Per2^−/− mice was less apparent in Per2^−/−/Pml^−/− mice. Both the Per1^−/−/Pml^−/− and Per2^−/−/Pml^−/− mice displayed a more advanced phase angle of entrainment activity during light–dark cycles than the single gene deficient mice.

Conclusions: Beyond merely regulating PER1 and PER2, the current behavioral studies suggest PML has additional roles in mouse circadian behavior.

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Published

2013-08-28

Issue

Vol. 11 (2013)

Section

Research Article

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