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

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 for'Per2'−/− 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.

Keywords

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