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

Takao Miki1, Misty Chen-Goodspeed, Zhaoyang Zhao

  • 1Department of Biochemistry and Molecular Biology, Medical School, University of Texas Health Science Center-Houston, Houston, TX, 77030, USA. Cheng.C.Lee@uth.tmc.edu.

Journal of Circadian Rhythms
|August 30, 2013
PubMed
Abstract

Insights

Promyelocytic leukemia (PML) influences mouse circadian rhythms. PML deficiency in Per1-/- mice shortens their rhythm, while in Per2-/- mice, it further disrupts rhythmicity, indicating PML

Area of Science:

  • Chronobiology
  • Molecular Biology
  • Genetics

Background:

  • The promyelocytic leukemia (PML) gene, a homolog of a human tumor suppressor, is implicated in regulating circadian behavior in mice.
  • Previous research suggests PML's role in circadian rhythm regulation.

Purpose of the Study:

  • To investigate the specific contribution of PML to circadian behavior.
  • To analyze the behavioral phenotypes of mice lacking both PML and either Period 1 (Per1) or Period 2 (Per2) genes.

Main Methods:

  • Generation of Per1-/-/Pml-/- and Per2-/-/Pml-/- mouse models.
  • Wheel-running behavioral analysis in free-running and light-dark cycle conditions.
  • Assessment of phase response to light pulses at specific zeitgeber times (ZT).

Main Results:

  • Per1-/-/Pml-/- mice exhibited a maintained but shorter circadian period (22.2 h) and enhanced phase response to light.
  • Per2-/-/Pml-/- mice lost persistent rhythm in free-running conditions, with diminished transient rhythmicity post-light pulse compared to Per2-/- mice.
  • Both Per1-/-/Pml-/- and Per2-/-/Pml-/- mice showed an advanced phase angle of entrainment during light-dark cycles compared to single gene-deficient mice.

Conclusions:

  • PML plays a significant role in mouse circadian behavior beyond its regulation of PER1 and PER2.
  • These findings highlight novel functions of PML in the molecular clockwork and behavioral output.

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