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 (Clock(Δ19/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 Clock(Δ19/Δ19) mice 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 Clock(Δ19/Δ19) and WT mice. Clock(Δ19/Δ19) mice 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 Clock(Δ19/Δ19) mice. Additionally, functional bladder capacity was significantly lower in Clock(Δ19/Δ19) mice than in WT mice.
We demonstrated that Clock(Δ19/Δ19) mice showed the phenotype of NOC/NP. The Clock(Δ19/Δ19) mouse may be used as an animal model of NOC and NP. Neurourol. Urodynam. © 2016 Wiley Periodicals, Inc.
Neurourology and urodynamics. 2016 Jun 27 [Epub ahead of print]
Tatsuya Ihara, Takahiko Mitsui, Yuki Nakamura, Satoru Kira, Tatsuya Miyamoto, Hiroshi Nakagomi, Norifumi Sawada, Yuri Hirayama, Keisuke Shibata, Eiji Shigetomi, Yoichi Shinozaki, Mitsuharu Yoshiyama, Karl-Erik Andersson, Atsuhito Nakao, Masayuki Takeda, Schuichi Koizumi
Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Immunology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Institute for Regenerative Medicine, Wake Forest University, Winston Salem, North Carolina., Department of Immunology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.