Presence of multiple peripheral circadian oscillators in the tissues controlling voiding function in mice

Jong Yun Noh, Dong Hee Han, Mi Hee Kim, Il Gyu Ko, Sung Eun Kim, Noheon Park, Han Kyoung Choe, Khae Hawn Kim, Kyungjin Kim, Chang Ju Kim, Sehyung Cho

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In the present study, we demonstrate that Per2 promoter activity clearly oscillates in neonate and adult bladders cultured ex vivo from Per2::Luc knock-in mice. In subsequent experiments, we show that multiple local oscillators are operating in all the bladder tissues (detrusor, sphincter and urothelim) and the lumbar spinal cord (L4-5) but not in the pontine micturition center or the ventrolateral periaqueductal gray of the brain. Accordingly, the water intake and urine volume exhibited daily and circadian variations in young adult wild-type mice but not in Per1-/-Per2-/- mice, suggesting a functional clock-dependent nature of the micturition rhythm. Particularly in PDK mice, the water intake and urinary excretion displayed an arrhythmic pattern under constant darkness, and the amount of water consumed and excreted significantly increased compared with those of WT mice. These results suggest that local circadian clocks reside in three types of bladder tissue and the lumbar spinal cord and may have important roles in the circadian control of micturition function.

Original languageEnglish (US)
Article numbere81
JournalExperimental and Molecular Medicine
Issue number3
StatePublished - Mar 2014
Externally publishedYes


  • Bladder
  • Circadian clock
  • Lumbar spinal cord
  • Peripheral oscillator
  • Voiding
  • Water intake

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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