The Suprachiasmatic Nucleus (SCN) is the main regulator of many biological rhythms in mammals and synchronizes the rest of the organism to the light-dark cycle. Disruption of this synchronization, as happens during shift work, jet lag, and old age, results in a serious impact on human health. Therefore an important area of study is the interaction between the SCN, other brain areas, and body tissues with respect to various circadian rhythms. By making a tetracycline-regulated knock-out of a core clock gene, Bmal1, in the SCN and some brain areas, this research proposal will address whether loss of Bmal1 in these areas in an adult mouse will abolish circadian rhythms of locomotor activity as well as synchrony of mPER2::LUC oscillations in peripheral tissues. This conditional Bmal1 knock-out can also be used for future studies of central regulation of liver entrainment as well as whether Bmal1 in these brain areas is involved in methamphetamine-induced anticipatory locomotor activity. Finally Bmal1 is involved in non-circadian abnormalities such as arthropathy and reproductive impairment, and the Bmal1 knock-out proposed here will be helpful for future studies distinguishing the roles of central and peripheral Bmal1 in these phenotypes.
| Izumo, Mariko; Pejchal, Martina; Schook, Andrew C et al. (2014) Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant. Elife 3: |
