distinct functions of period2 and period3 in the mouse circadian system revealed by in vitro analysis不同功能period2和period3鼠标昼夜系统揭示了体外分析.pdfVIP

Distinct Functions of Period2 and Period3 in the Mouse Circadian System Revealed by In Vitro Analysis Julie S. Pendergast, Rio C. Friday, Shin Yamazaki* Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America Abstract The mammalian circadian system, which is composed of a master pacemaker in the suprachiasmatic nuclei (SCN) as well as other oscillators in the brain and peripheral tissues, controls daily rhythms of behavior and physiology. Lesions of the SCN abolish circadian rhythms of locomotor activity and transplants of fetal SCN tissue restore rhythmic behavior with the periodicity of the donor’s genotype, suggesting that the SCN determines the period of the circadian behavioral rhythm. According to the model of timekeeping in the SCN, the Period (Per) genes are important elements of the transcriptional/ translational feedback loops that generate the endogenous circadian rhythm. Previous studies have investigated the functions of the Per genes by examining locomotor activity in mice lacking functional PERIOD proteins. Variable behavioral phenotypes were observed depending on the line and genetic background of the mice. In the current study we assessed both wheel-running activity and Per1-promoter-driven luciferase expression (Per1-luc) in cultured SCN, pituitary, and lung explants from Per22/ 2 and Per32/ 2 mice congenic with the C57BL/6J strain. We found that the Per22/ 2 phenotype is enhanced in vitro compared to in vivo, such that the period of Per1-luc expression in Per22/ 2 SCN explants is 1.5 hours shorter than in Per2+/+ SCN, while the free-running period of wheel-running activity is only 11 minutes shorter in Per22/ 2 compared to Per2+/+ mice. In contrast, circadian rhythms in SCN explants from Per32/ 2 mice do not differ from Per3+/+ mice. I