Genetic and Physiological Studies of Circadian Mutant Mice

我们尝试用正向遗传学方法寻找小鼠的昼夜节律突变。本研究试图从生理学的角度来鉴定导致这些小鼠昼夜节律异常的基因，并对这些小鼠的昼夜节律进行表征。(1)CS小鼠：利用QTL分析，我们已经定位了染色体上影响昼夜节律周期的QTL。根据定位信息，寻找候选基因，发现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，以确定该基因是否与异常有关。(2)心律失常小鼠：我们在栗属野生小鼠群体中发现了心律失常突变。在此，我们还通过QTL遗传分析定位了导致异常节律的基因。在这些心律失常小鼠中，视交叉上核中几个时钟基因的表达与正常小鼠没有很大差异。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没有明显的组织学差异。(3)CBA/J小鼠具有较低的昼夜光敏感性。影响昼夜光敏感性的基因被定位在染色体上。现在，我们正在检查候选基因的ORF。其他研究涉及使用SMXA的昼夜节律周期的遗传分析，我们已经发现了另一种昼夜节律突变小鼠，其在DD中显示出紊乱的昼夜节律。为了将来的研究，现在正在进行育种。

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.