Graduate Student- MD PhD

Neurobiology and Physiology

Northwestern University (Evanston, IL)

Joseph S Takahashi

Loss of Bmal1 in the mouse SCN/brain: effect on locomotor activity and rhythms of peripheral circadian gene expression

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. We have made a knock-out of a core clock gene, Bmal1, in the SCN and some brain areas, and this knock-out shows an immediate and complete loss of circadian rhythmicity in constant darkness. These are the first experiments to successfully knockout a circadian clock gene in the SCN/brain and to produce an arrhythmic phenotype. At present we are studying how rhythms of peripheral circadian genes are affected in this knock-out using in situ, Westerns, and luminescence recording. This local 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 made here will be helpful for future studies distinguishing the roles of central and peripheral Bmal1 in these phenotypes.

2006-2011 Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship