Genetic and Physiological Studies of Circadian Mutant Mice

昼夜节律突变小鼠的遗传和生理学研究

基本信息

批准号：
10460130
负责人：
EBIHARA Shizufumi
金额：
$ 3.46万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10460130/
关键词：
circadian rhythm mice genetics mutation QTL analysis QTL解析概日リズム遺伝解析 QTL

项目摘要

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.

我们尝试基于正向遗传方法寻找小鼠的昼夜节律突变。结果，发现了几只表现出昼夜节律异常的小鼠。在这项研究中，我们试图找出导致节律异常的基因，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，我们在染色体上绘制了影响昼夜节律的QTL。根据定位信息对候选基因进行搜索，发现了1个在视交叉上核中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异常。 (2)心律失常小鼠：我们发现栗野生小鼠群体存在心律失常突变。同样在这里，我们通过 QTL 遗传分析绘制了导致节律异常的基因图谱。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没有明显的组织学差异。 (3)昼夜节律光敏感性较低的CBA/J小鼠。影响昼夜节律光敏性的基因被映射在染色体上。现在，我们正在检查候选基因的ORF。其他研究涉及使用 SMXA 对昼夜节律进行遗传分析，我们发现了另一种昼夜节律突变小鼠，其在 DD 中表现出紊乱的昼夜节律。为了将来的研究，目前正在进行育种。