Mutagenesis and behavioral screening for altered circadian activity identifies the mouse mutant, Wheels
Related Experiment Video
Updated: Nov 4, 2026
Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents
Published on: January 24, 2013
G E Pickard1, P J Sollars, E M Rinchik
1Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104-6141, USA.
Abstract:
The molecular processes underlying the generation of circadian behavior in mammals are virtually unknown. To identify genes that regulate or alter circadian activity rhythms, a mouse mutagenesis program was initiated in conjunction with behavioral screening for alterations in circadian period (tau), a fundamental property of the biological clock. Male mice of the inbred BALB/c strain, treated with the potent mutagen N-ethyl-N-nitrosourea were mated with wild-type hybrids. Wheel-running activity of approximately 300 male progeny was monitored for 6-10 weeks under constant dark (DD) conditions. The tau DD of a single mouse (#187) was longer than the population mean by more than three standard deviations (24.20 vs. 23.32 +/- 0.02 h; mean +/- S.E.M.; n = 277). In addition, mouse #187 exhibited other abnormal phenotypes, including hyperactive bi-directional circling/spinning activity and an abnormal response to light. Heterozygous progeny of the founder mouse, generated from outcrossings with wild-type C57BL/6J mice, displayed lengthened tau DD although approximately 20% of the animals showed no wheel-running activity despite being quite active. Under light:dark conditions, all animals displaying circling behavior that ran in the activity wheels exhibited robust wheel-running activity at lights-ON and these animals also showed enhanced wheel-running activity in constant light conditions. The genetic dissection of the complex behavior associated with this mutation was facilitated by the previously described genetic mapping of the mutant locus causing circling behavior, designated Wheels (Whl), to the subcentromeric portion of mouse chromosome 4. In this report, the same locus is shown to be responsible for the abnormal responses to light and presumably for the altered circadian behavior. Characterization of the gene altered in the novel Whl mutation will contribute to understanding the molecular elements involved in mammalian circadian regulation.
Insights
Researchers identified a novel mouse mutation, Wheels (Whl), affecting circadian rhythms and activity. This mutation alters the circadian period and causes abnormal circling and light responses, offering insights into mammalian biological clock regulation.
Area of Science:
- Neuroscience
- Genetics
- Chronobiology
Background:
- The molecular mechanisms governing mammalian circadian behavior remain largely unelucidated.
- Circadian rhythms, fundamental biological clocks, regulate daily physiological and behavioral cycles.
Purpose of the Study:
- To identify genes influencing circadian activity rhythms in mammals.
- To characterize a novel mutation affecting circadian period and behavior.
Main Methods:
- A mouse mutagenesis program using N-ethyl-N-nitrosourea was employed.
- Behavioral screening of approximately 300 male progeny monitored wheel-running activity under constant dark conditions.
- Genetic mapping of the mutant locus to mouse chromosome 4.
Main Results:
- A single mouse (#187) exhibited a significantly lengthened circadian period (tau DD) and abnormal circling/spinning behavior.
- Heterozygous progeny also displayed lengthened tau DD, with some showing no wheel-running activity despite high activity levels.
- The Wheels (Whl) locus on mouse chromosome 4 was linked to altered circadian behavior, circling, and abnormal light responses.
Conclusions:
- The novel Wheels (Whl) mutation provides a valuable tool for dissecting the genetic basis of mammalian circadian regulation.
- Characterization of the gene affected by the Whl mutation is crucial for understanding the molecular components of the biological clock.
