Ontogeny of unique circadian rhythm in rhythm mutant mice

CS小鼠在持续的黑暗中表现出昼夜行为节律的自发分裂。为了阐明CS小鼠节律分裂的个体发育，对CS成鼠和幼鼠的行为节律和时钟基因节律进行了研究。在行为节律上，P21仔鼠在LD周期下表现为分裂模式。由C57BL/6J的养母在出生后饲养的CS仔鼠也表现出明显的分裂模式。在时钟基因节律方面，用原位杂交方法检测了CS P13和P21仔鼠SCN和其他脑区的PER1和PER2基因节律。数据目前正在分析中。为了比较CS节律的个体发育与大鼠的节律，我们研究了大鼠SCN中时钟基因节律的个体发育。结果表明，P6仔鼠的PER1和PER2节律受到母亲节律的影响，出生后第一周周期性地没有哺乳母亲会使幼鼠节律的相位发生改变。为了阐明脑组胺在生物钟系统中的功能作用，对组氨酸脱羧酶缺陷小鼠(HDC小鼠)的行为节律和时钟基因节律进行了研究。在行为节律上，HDC小鼠在LD和DD条件下表现出较低的活动水平，在DD条件下表现出较长的自由奔跑时间。在时钟基因节律上，HDC小鼠和野生型小鼠SCN的PER1和PER2节律没有差异。而大脑皮层、纹状体等其他脑区的PER1和PER2无节律或抑制振荡。这些结果表明，脑组胺参与了SCN起搏器的输出机制。

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.