Behavioral characterization and modulation of circadian rhythms by light and melatonin in C3H/HeN mice homozygous for

Monica I Masana1, Isabel C Sumaya, Michael Becker-Andre

  • 1Department of Molecular Pharmacology and Biological Chemistry Northwestern University Feinberg School of Medicine, Chicago, IL 60611-3008, USA.

Insights

Retinoid-related orphan receptor beta (RORbeta) gene deletion in mice impacts motor and olfactory functions, and anxiety. While not affecting melatonin rhythms, RORbeta influences circadian clock responses to light.

Area of Science:

  • Neuroscience
  • Chronobiology
  • Genetics

Background:

  • Retinoid-related orphan receptors (RORs) are nuclear receptors involved in various biological processes.
  • RORbeta's role in behavioral and circadian phenotypes remains largely unexplored.

Purpose of the Study:

  • To investigate the effects of RORbeta gene deletion on behavioral and circadian phenotypes in C3H/HeN mice.

Main Methods:

  • Generation of RORbeta knockout mice (RORbeta(C3H)(-/-)).
  • Assessment of behavioral phenotypes (motor, olfactory, anxiety, learned helplessness).
  • Analysis of circadian activity rhythms, melatonin levels, and responses to light and melatonin stimuli.

Main Results:

  • RORbeta(C3H)(-/-) mice exhibited motor deficits (duck gait, hind paw clasping) and olfactory deficits.
  • These mice showed reduced anxiety and learned helplessness behaviors.
  • Circadian period (tau) was significantly increased in RORbeta(C3H)(-/-) mice.
  • While melatonin production was unaffected, RORbeta deletion altered responses to light stimuli at specific circadian times.

Conclusions:

  • RORbeta is not essential for rhythmic pineal melatonin production or melatonin-mediated phase shifts.
  • RORbeta plays a role in regulating clock responses to photic stimuli, particularly at late circadian times.
  • RORbeta influences motor, olfactory, and anxiety-related behaviors.

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