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

Abstract

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.