A recessive mutant of Drosophila Clock reveals a role in circadian rhythm amplitude

A recessive mutant of Drosophila Clock reveals a role in circadian rhythm amplitude
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DOI:
10.1093/emboj/cdg318
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发表时间:
2003-07-01
期刊:
影响因子:
11.4
通讯作者:
Rosbash, M
Rosbash, M
中科院分区:
生物学1区
文献类型:
--
作者:
Allada, R;Kadener, S;Rosbash, M

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转录因子Clock(Clk)在动物昼夜节律中起着关键作用。定义其功能的遗传学研究依赖于两个显性负等位基因,一个在果蝇中,一个在小鼠中。在这里,我们描述了一个新的隐性等位基因的果蝇时钟,Clk(ar)。纯合子Clk(ar)果蝇是可存活的并且行为上是寄生的。Clk(ar)表型由严重破坏剪接并降低Clk活性的剪接位点突变引起。尽管Clk(ar)果蝇的行为不稳定,但仍能检测到分子振荡。转录分析表明Clk(ar)对转录振荡的水平和幅度具有强作用。与其他数据一起,我们提出,Clk作出了重大贡献的强度和幅度的昼夜节律。
The transcription factor Clock (Clk) plays a critical role in animal circadian rhythms. Genetic studies defining its function have relied on two dominant negative alleles, one in Drosophila and one in mice. Here we describe a novel recessive allele of Drosophila Clock, Clk(ar). Homozygous Clk(ar) flies are viable and behaviorally arrhythmic. The Clk(ar) phenotype is caused by a splice site mutation that severely disrupts splicing and reduces Clk activity. Despite the behavioral arrhythmicity, molecular oscillations are still detectable in Clk(ar) flies. Transcription analysis indicates potent effects of Clk(ar) on levels and amplitude of transcriptional oscillations. Taken together with other data, we propose that Clk makes a major contribution to the strength and amplitude of circadian rhythms.