Ontogeny of unique circadian rhythm in rhythm mutant mice

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CS mice show spontaneous splitting in the circadian rhythm of behavior under continuous darkness. To clarify ontogeny of rhythm splitting in the CS mice, the behavioral rhythm and clock gene rhythm in the brain of CS adult and pups were examined. In the behavioral rhythm, P21 pups showed splitting pattern under LD cycle. CS pups, which were reared by foster mother of C57BL/6J after birth, also showed clear split pattern. In the clock gene rhythm, Per1 and Per2 mRNA rhythms in the SCN and other brain areas of CS P13 and P21 pups were examined by in situ hybridization. Data are currently being analyzed.To compare the ontogeny of CS's rhythm with that of rats, ontogeny of clock gene rhythm in the SCN of rats were examined. The results showed that Per1 and Per2 rhythms of P6 pups were influenced by mother's rhythm, and that the phases of the pup rhythms were shifted by periodic absence of nursing mother for the first week after birth.To clarify the functional role of brain histamine in the circadian clock system, the behavioral rhythm and clock gene rhythm in the brain of histidine decarboxylase deficient mice (HDC mice) were examined. In the behavioral rhythm, HDC mice showed low activity level under LD and DD, and prolonged freerunning period under DD. In the clock gene rhythm, there was no difference in the Per1 and Per2 rhythms in the SCN of HDC mice from that of wild type mice. However, the Per1 and Per2 in the other brain areas such as cerebral cortex and striatum showed no rhythm or damped oscillation. These results suggest that brain histamine is involved in the output mechanism from the SCN pacemaker.