Early-to-Bed Mice Offer Window into Sleep Disorders, Other Conditions

By Jennifer O'Brien

UCSF neuroscientists Louis Ptáček, MD, Ying-Hui Fu, PhD, and colleagues are exploring the body's biological rhythms. Sometimes these are referred to as "clocks," and at other times as circadian rhythms. The goal of their research is to understand the nature of sleep, as well as the impact that disruptions of circadian rhythms have on the body. Circadian rhythms are a waxing and waning of genetic, biochemical and physiological processes that occur in a 24-hour period. They help regulate daily changes in alertness and cognitive function, heart rate and blood pressure, the immune system and the digestive system function, among other processes. Scientists know little about these rhythms at the molecular level, but evidence suggests that disruptions in their regulation may affect disease processes, possibly provoking or exacerbating asthma attacks and migraines, contributing to breast cancer risk and affecting the response of breast cancers to treatment, says Ptáček. Previously, the scientists reported the discovery of mutated genes that cause a rare sleep behavior in which people have a "fast" biological clock (Science, Feb. 9, 2001; Nature, March 31, 2005). People in families with this disorder go to bed earlier than normal (around 7:30 p.m.) and wake up earlier than normal (typically before 4:30 a.m.). Now, the team has genetically engineered mice to express one of the mutated human genes. Instead of scurrying around at night and sleeping all day, these mice snuggle up in the evening and forage during the day (Cell, Jan. 12, 2007). As such, says Ptáček, they offer a window into the impact of disruptions in circadian rhythms on sleep. More broadly, he says, they offer a tool for illuminating the broader effect of disruptions in circadian rhythms on human disease and behaviors. Ptáček, who holds the John C. Coleman Distinguished Professorship in Neurodegenerative Diseases at UCSF, is also a Howard Hughes Medical Institute Investigator. Fu is professor of neurology. For a lay description of Ptáček and Fu's latest finding, see Howard Hughes Medical Institute news release.

Modeling of a Human Circadian Mutation Yields Insight into Clock Regulation by PER2 Y. Xu, K.L. Toh, C.R. Jones, J.-Y. Shin, Y.-H. Fu, and L.J. Ptáček Cell, January 12, 2007; 128:59-70 Abstract | Full Text | Full Text (PDF)
Functional consequences of a CKI-delta mutation causing familial advanced sleep phase syndrome Ying Xu, Quasar S. Padiath, Robert E. Shapiro, Christopher R. Jones, Susan C. Wu, Noriko Saigoh, Kazumasa Saigoh, Louis J. Ptáček, and Ying-Hui Fu Nature, March 31, 2005; 434:640-644 Full Text | Full Text (PDF)
An hPer2 Phosphorylation Site Mutation in Familial Advanced Phase Sleep Syndrome Kong L. Toh, Christopher R. Jones, Yan He, Erik J. Eide, William A. Hinz, David M. Virshup, Louis J. Ptáček, Ying-Hui Fu Science, February 9, 2001; 291(5506):1040-1043 Abstract | Full Text | Full Text (PDF)

Related links: Early-to-Bed Mouse Illuminates Workings of Circadian Clock Howard Hughes Medical Institute News Release, January 12, 2007 Sleeping Really Strange Hours? Maybe a Rogue Gene Is to Blame UCSF Today, June 12, 2006 UCSF Study Offers Insight into Human Circadian Rhythms UCSF News Release, March 30, 2005 Fu and Ptáček's Laboratories of Neurogenetics UCSF Department of Neurology

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