Clock Gene and Gene Product

Genetic Control of Mammalian Circadian Rhythms: Sequence, Function, and Utility of the Clock Gene and its Product NU 1997-008, 1997-050 and 1998-033 Inventors Joseph S. Takahashi Fred W. Turek Lawrence H Pinto Abstract Northwestern researchers have discovered a gene in mice and humans that regulates both the periodicity and the persistence of circadian rhythms. The circadian clock regulates a daily cycle of physical and chemical processes in all eukaryotes and most prokaryotes. This cycle is known to be genetically controlled and to involve periodic macromolecular synthesis, but the elements responsible for circadian rhythmicity in mammals have previously been unknown. Pharmaceutical manipulation of CLOCK expression or activity is expected to alter the level and the timing of the transcription of mper 1 and probably of other genes, thereby altering the circadian cycle. Furthermore, the Clock gene and its product can be used to identify other proteins that control the function of CLOCK and genes that respond to its activity as a transcription factor. Other pathways known to influence circadian rhythm, such as neurotransmitters, hormones, second messengers, and immediate early genes, have diverse, non-specific functions and act throughout the body. However, mutations of the Clock gene which have severe consequences on circadian phenotypes have no other discernible effect on the metabolism or behavior of the organism indicating that clock and its partners can be specifically targeted for using pharmacological approaches for regulating circadian rhythms in mammals. APPLICATIONS Pharmaceutical control of circadian rhythms: o Sleep/wake cycle (e.g. shift work, jet lag, and sleep disorders) o Other physical processes that respond to the circadian cycle (e.g. drug responsiveness, mental and cardiovascular disorders, hormonal variations, and feeding behavior) ADVANTAGES Specific targeting of circadian phenotypes PUBLICATIONS Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, Takahashi JS (1994) Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science. 264: 719-25. IP STATUS Issued US Patent Nos. 5,874,241; 6,057,125; 6,291,429 MARKETING CONTACT Becky Crump, PhD Associate Director (e) [email protected] (p) 847.491.3630