Effects of the<i>Duper</i>Mutation on Circadian Responses to Light

Krug, Stefanie; Brewer, Judy McKinley; Bois, Alexandre S.; Bittman, Eric L.

doi:10.1177/0748730411411570

Cited by 11 publications

(52 citation statements)

References 42 publications

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“…It is possible that shifts in response to a DD to LL transition during subjective day (during the dead zone of the PRC for light pulses) are not immediate but are triggered by an effect of light after the start of subjective night. However, dupers experienced larger phase shifts in response to a DD to LL transition at CT 9 or 12 than they did to a 15-min light pulse at CT 12 (Krug et al, 2011). …”

Section: Discussionmentioning

confidence: 88%

“…The profound differences between duper and WT hamsters in responses to transfer between LL and DD (experiments 2 and 3) greatly complicate interpretation of Aschoff type II designs in experiments on nonphotic phase shifting. Furthermore, the short period of duper hamsters results in a more positive phase angle and greater masking in LD cycles (Krug et al, 2011). This complicates assessment of the circadian phase at which the nonphotic stimulus is provided and makes comparison of duper and WT responses still more difficult.…”

Section: Discussionmentioning

confidence: 99%

“…An effect of duper to reduce oscillator amplitude (Krug et al, 2011) may also explain increased variability in phase shifts. Exaggerated responses of core clock components downstream from the perturbation of Per1 may contribute to or account for variability and lability of resetting.…”

Section: Discussionmentioning

confidence: 99%

“…All hamsters were derived from stock obtained from Lakeview (LAK:LVG) and have been bred in our laboratory for multiple generations as previously described (Monecke et al, 2011). As adults, animals were housed individually with continuous access to a running wheel (17.5 cm diameter) as previously described (Krug et al, 2011). To minimize artifactual changes in phase and period, cages and water bottles were changed every 30 days during experiment 1 and every 10 to 20 days in experiments 2 and 3.…”

Section: Methodsmentioning

confidence: 99%

“…Although the duper mutation has no effect on the precision or stability of activity rhythms in constant darkness (DD; Bittman, 2012), it markedly amplifies phase-shifting responses to 15-min light pulses (Krug et al, 2011). The effect of duper on responses to nonphotic zeitgebers is not yet known.…”

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confidence: 99%

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Phase Resetting in Duper Hamsters

2015

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The duper mutation in Syrian hamsters shortens the free-running period of locomotor activity (τDD) to about 23 h and results in a type 0 phase-response curve (PRC) to 15-min light pulses. To determine whether exaggerated phase shifts are specific to photic cues and/or restricted to subjective night, we subjected hamsters to novel wheel confinements and dark pulses during subjective day. Small phase shifts elicited by the nonphotic cue were comparable in mutant and wild-type (WT) hamsters, but dark pulses triggered larger shifts in dupers. To assess further the effects of the duper mutation on light-dark transitions, we transferred hamsters between constant light (LL) and constant dark (DD) or between DD and LL at various circadian phases. Duper hamsters displayed significantly larger phase shifts than WT hamsters when transferred from LL to DD during subjective day and from DD to LL during subjective night. The variability of phase shifts in response to all light/dark transitions was significantly greater in duper hamsters at all time points. In addition, most duper hamsters, but none of the WTs, displayed transient ultradian wheel-running patterns for 5 to 12 days when transferred from light to dark at CT 18. The χ2 periodogram and autocorrelation analyses indicate that these ultradian patterns differ from the disruption of rhythmicity by SCN lesions or exposure to constant bright light. We conclude that the duper mutation specifically amplifies phase shifts to photic cues and may destabilize coupling of circadian organization upon photic challenge due to weakened coupling among components of the circadian pacemaker. Mathematical modeling of the circadian pacemaker supports this hypothesis.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Phase Resetting in Duper Hamsters

2015

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The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease

Sisson

Bahiru

Manoogian

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The Cryptochrome 1 ( Cry1 )–deficient duper mutant hamster has a short free-running period in constant darkness (τ DD ) and shows large phase shifts in response to brief light pulses. We tested whether this measure of the lability of the circadian phase is a general characteristic of Cry1 -null animals and whether it indicates resistance to jet lag. Upon advance of the light:dark (LD) cycle, both duper hamsters and Cry1 −/− mice re-entrained locomotor rhythms three times as fast as wild types. However, accelerated re-entrainment was dissociated from the amplified phase-response curve (PRC): unlike duper hamsters, Cry1 −/− mice show no amplification of the phase response to 15’ light pulses. Neither the amplified acute shifts nor the increased rate of re-entrainment in duper mutants is due to acceleration of the circadian clock: when mutants drank heavy water to lengthen the period, these aspects of the phenotype persisted. In light of the health consequences of circadian misalignment, we examined effects of duper and phase shifts on a hamster model of heart disease previously shown to be aggravated by repeated phase shifts. The mutation shortened the lifespan of cardiomyopathic hamsters relative to wild types, but this effect was eliminated when mutants experienced 8-h phase shifts every second week, to which they rapidly re-entrained. Our results reveal previously unsuspected roles of Cry1 in phase shifting and longevity in the face of heart disease. The duper mutant offers new opportunities to understand the basis of circadian disruption and jet lag.

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duperis a null mutation of Cryptochrome 1 in Syrian hamsters

Lee

Cal-Kayitmazbatir

Francey

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance We successfully identified the duper allele as a null mutation of Cryptochrome 1 in Syrian hamsters. Here, we have shown the use of fast homozygosity mapping as an effective approach to identify causal mutations in mammals, despite lacking chromosomal genome information. In the course of this work, we improved the draft Syrian hamster genome and generated datasets necessary to exploit Syrian hamsters as a modern genetic research model. The unique physiological features of Syrian hamsters make them a desirable model to investigate human diseases, including circadian disorders, cancer, heart function, metabolism, and infectious diseases (e.g., severe acute respiratory syndrome coronavirus 2).

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Effects of theDuperMutation on Circadian Responses to Light

Cited by 11 publications

References 42 publications

Phase Resetting in Duper Hamsters

Phase Resetting in Duper Hamsters

The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease

duperis a null mutation of Cryptochrome 1 in Syrian hamsters

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