Genetic and Physiological Studies of Circadian Mutant Mice

我们试图基于正向遗传方法在小鼠身上发现昼夜节律突变。结果，发现了几只表现出异常昼夜节律的小鼠。在这项研究中，我们试图找出导致异常节律性的基因，并从生理学的角度描述这些小鼠的昼夜节律。(1)CS小鼠：通过QTL分析，在染色体上定位了影响昼夜节律的QTL。根据定位信息，搜索候选基因，找到一个在视交叉上核表达的潜在候选基因。目前，实验正在进行中，以确定该基因是否导致了这种异常。(2)心律失常小鼠：我们发现心律失常突变是卡氏野鼠种群。并通过QTL遗传分析定位了与异常节律性相关的基因。在这些心律失常的小鼠中，视交叉上核中的几个时钟基因的表达与正常小鼠没有太大差异。因此推测该基因可能影响生物钟的输出途径。事实上，这些小鼠的视交叉上核在组织学上没有明显的差异。(3)昼夜光敏性较低的CBA/J小鼠。影响昼夜节律光敏的基因被定位在染色体上。现在，我们正在检测候选基因的ORF。其他研究包括利用SMXA对昼夜节律的遗传分析，我们发现了另一只昼夜节律突变的小鼠，它在DD中表现出紊乱的昼夜节律。为了将来的研究，育种工作正在进行中。

We have tried to find circadian mutation in mice based on the forward genetic approach. As a result, several mice showing abnormal circadian rhythmicity were found. In this study, we have tried to identify the gene which is responsible for the abnormal rhythmicity and also characterize the circadian rhythm of these mice from a physiolocia standpoint. (1) CS mice : Using QTL analysis we have mapped the QTL affecting circadian period on chromosomes. Based on the mapping information, candidate genes were searched and one potential candidate gene which is expressed in the suprachiasmatic nucleus was found. At present, the experiment is in progress to determine if the gene is responsible for the abnormality. (2) Arrythmic mice : We have found arrythmic mutation is castaneus wild mouse population. Also here, we have mapped the genes responsible the abnormal rhythmicity by QTL genetic analysis. In these arrythmic mice, the expression of several clock genes in the suprachiasmatic nucleus is not very different from normal mice. Therefore it is speculated that the gene might affect the output pathway from the circadian clock. In fact, there are no obvious histological differences in the suprachiasmatic nucleus of these mice. (3) CBA/J mice which have lower circadian photosensitivity. The genes affecting circadian photosensitivity are mapped on chromosomes. Now, we are examining ORF of the candidate gene. Other studies involve genetic analysis of circadian period using SMXA, we have found another circadian mutant mouse which shows disorganized circadian rhythmicity in DD. For future study, the breeding is now in progress.