title: The Clock mutant mouse is a novel experimental model for nocturia and nocturnal polyuria.
abstract: The pathophysiologies of nocturia (NOC) and nocturnal polyuria (NP) are multifactorial and their etiologies remain unclear in a large number of patients. Clock genes exist in most cells and organs, and the products of Clock regulate circadian rhythms as representative clock genes. Clock genes regulate lower urinary tract function, and a newly suggested concept is that abnormalities in clock genes cause lower urinary tract symptoms. In the present study, we investigated the voiding behavior of Clock mutant (ClockΔ19/Δ19) mice in order to determine the effects of clock genes on NOC/NP.
  
  
  
  Male C57BL/6 mice aged 8-12 weeks (WT) and male C57BL/6 ClockΔ19/Δ19mice aged 8 weeks were used. They were bred under 12 hr light/dark conditions for 2 weeks and voiding behavior was investigated by measuring water intake volume, urine volume, urine volume/void, and voiding frequency in metabolic cages in the dark and light periods.
  
  
  
  No significant differences were observed in behavior patterns between ClockΔ19/Δ19and WT mice. ClockΔ19/Δ19mice showed greater voiding frequencies and urine volumes during the sleep phase than WT mice. The diurnal change in urine volume/void between the dark and light periods in WT mice was absent in ClockΔ19/Δ19mice. Additionally, functional bladder capacity was significantly lower in ClockΔ19/Δ19mice than in WT mice.
  
  
  
  We demonstrated that ClockΔ19/Δ19mice showed the phenotype of NOC/NP. The ClockΔ19/Δ19mouse may be used as an animal model of NOC and NP. Neurourol. Urodynam. 36:1034-1038, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ihara
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Mitsui
authors.affiliation: Department of Immunology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kira
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagomi
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Sawada
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Hirayama
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shigetomi
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinozaki
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Yoshiyama
authors.affiliation: Institute for Regenerative Medicine, Wake Forest University, Winston Salem, North Carolina.
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.affiliation: Department of Immunology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Schuichi
authors.initials: S
authors.lastname: Koizumi
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053158:Nocturia / Q000235:genetics*; D011141:Polyuria / Q000235:genetics*
chemical_list: D056926:CLOCK Proteins; C538944:Clock protein, mouse
keywords: clock gene; noctrunal polyuria; nocturia