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

Aug 5, 2022Proceedings of the National Academy of Sciences of the United States of America

The duper mutation reveals new roles of Cryptochrome 1 in body clock adjustment and heart disease

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Abstract

Duper mutant hamsters re-entrain locomotor rhythms three times as fast as wild-type hamsters following light:dark cycle advances.

  • Duper mutant hamsters have a short free-running period in constant darkness and exhibit large phase shifts to brief light pulses.
  • The accelerated observed in duper hamsters is not linked to an amplified phase-response curve as seen in mice.
  • Both duper hamsters and mice show faster re-entrainment compared to wild types, but mice do not exhibit amplified responses to light.
  • The phenotype of accelerated re-entrainment in duper mutants remains despite lengthening the circadian period by drinking heavy water.
  • Duper mutation shortens the lifespan of cardiomyopathic hamsters, yet this effect is negated with regular 8-hour phase shifts.
  • Findings suggest complex interactions between phase shifting, longevity, and heart disease in the context of circadian disruption.

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Key numbers

Rate Increase
Duper hamsters re-entrain at least 3 times faster than wild types.
224 d vs. 335 d
Lifespan Comparison
Median age of death for duper hamsters vs. wild types.

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