CHEMICAL MUTAGENESIS IN MOUSE CIRCADIAN RHYTHMS

小鼠昼夜节律中的化学诱变

基本信息

批准号：
07557187
负责人：
EBIHARA Shizufumi
金额：
$ 1.6万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557187/
关键词：
circadian rhythm inbred strain mutation genetics chemical mutagenesis QTL wild mice クロラムプシル

项目摘要

Circadian rhythms which are driven by endogenous clocks with a period of approximately 24 hr under constant condition are observed in almost all creatures from procaryotes to mammals. The features of circadian rhythms are common to all species, but molecular mechanisms of circadian rhythms are unclear. The purpose of this study is to isolate circadian mutant in mice to understand molecular mechanisms of circadian rhythms. For this, we have used 3 different strategies. One is chemical mutagenesis, another is isolating a mutant from wild mice population and a third is a screening of inbred strains. Using this strategies, we have found several mutant mice which show abnormal rhythmicity. Furthermore, we have accidentally found another mutation in the course of breeding mice. The mutation found in wild mice population is characterized by loss of circadian rhythms under constant condition and shorter circadian period. Genetic analysis indicated that the arrythmic trait is recessive because … More F1 mice between the mutant and C57BL/6J show normal rhythms and the phenotype segregates in F2 and backcross. In the screening of inbred lines, CS mice were found to have abnormal circadian properties including longer free-running period, large activity phase, splitting of free-running rhythms in constant darkness. In order to identify chromosomal location of the genes influencing free-running period, we analyzed F2 progeny from the cross between CS and C57BL/6J mice by QTL (Quantitative trait locus) mapping method. As a result, three provisional regions on chromosomes 4 (LOD score=3.5), 12 (LOD score=3.4) and 19 (LOD score=3.7) were detected. These potential QTLs are investigated in another cross with MSM mice and it was found that the same region on chromosome 19 is detected with LOD score 4.2. These results suggest that the free-running period of CS mice is affected by multiple genes and particularly the QTL on chromosome 19 strongly affect the period. The last mutation found during the crossing of mice is characterized by suddenly disorganized rhythm and sometimes 8 hr periodicity under constant darkness. For future studies, this mutant mice were maintained with an appropriate breeding method. Less

在恒定条件下，在恒定条件下的内源性时钟驱动的昼夜节律在几乎所有从丙蜜核到哺乳动物的作品中都观察到。昼夜节律的特征对于所有物种都是共同的，但是昼夜节律的分子机制尚不清楚。这项研究的目的是分离小鼠中的昼夜节律突变体，以了解昼夜节律的分子机制。为此，我们使用了3种不同的策略。一种是化学诱变，另一个是从野生小鼠种群中分离出突变体的，三分之一是筛选近交菌株。使用这种策略，我们发现了几只突变小鼠，它们表现出异常的节奏性。此外，我们在繁殖小鼠过程中意外发现了另一个突变。在野生小鼠种群中发现的突变的特征是在恒定条件下散发节奏丧失，昼夜节律较短。遗传分析表明，芳香性性状是隐性的，因为……突变体和C57BL/6J之间更多的F1小鼠显示出正常的节奏，而表型在F2和反向杂音中分离。在筛选近交系列中，发现CS小鼠具有异常的昼夜节律特性，包括更长的自由运行时期，大活动阶段，在恒定的黑暗中分裂自由运行的节奏。为了鉴定基因的染色体位置影响自由运行时期，我们通过QTL（定量性状基因座）映射方法分析了F2从CS和C57BL/6J小鼠之间的杂交中进行进展。结果，检测到染色体4（LOD得分= 3.5），12（LOD分数= 3.4）和19（LOD得分= 3.7）的三个临时区域。这些潜在的QTL在与MSM小鼠的另一个十字架中进行了研究，发现与LOD评分4.2的同一区域相同的区域被检测到。这些结果表明，CS小鼠的自由运行时期受多个基因的影响，尤其是染色体19上的QTL强烈影响该时期。在小鼠穿越期间发现的最后一个突变的特征是在恒定的黑暗下突然杂乱无章的节奏，有时是8小时的周期性。对于将来的研究，使用适当的育种方法维持了这种突变小鼠。较少的