New mouse model of underactive bladder developed by placement of a metal ring around the bladder neck

Abstract

Objective To develop a new mouse model of underactive bladder (UAB) caused by chronic bladder outlet obstruction (BOO). Methods BOO was created in 6‐week‐old male C57BL/6 mice using surgery to loosely place a silver jump ring around the bladder neck of each mouse. Micturition behavior (assessed with a metabolic cage) and cystometry were used to evaluate bladder function at 8 and 16 weeks after BOO. Following completion of the functional studies, the bladders of the mice were excised, weighed, and subjected to histological analysis. Results Micturition behavior analysis showed that mice subjected to BOO for 16 weeks had a lower frequency of micturition (7.3 ± 1.1 vs 12.5 ± 3.0 times/d, P < .05) and volume per void (106.0 ± 0.1 vs 133.9 ± 3.2 μL, P < .05) than mice subjected to BOO for 8 weeks. Cystometry revealed that mice subjected to BOO for 16 weeks had lower baseline pressure (8.4 ± 0.6 vs 14.0 ± 0.7 cmH2O, P < .01) and micturition pressure (13.9 ± 1.1 vs 42.8 ± 1.7 cmH2O, P < .05) than mice subjected to BOO for 8 weeks. BOO caused progressive increases in bladder mass and collagen deposition over time. Conclusions We successfully established a novel mouse model of UAB using surgery to place a silver jump ring loosely on the bladder neck. BOO initially induced bladder overactivity but subsequently resulted in UAB due to deterioration of detrusor smooth muscle contractility and progressive deposition of collagen in the bladder wall.

Male Lower Urinary Tract Dysfunction: An Underrepresented Endpoint in Toxicology Research

“…Surgical approaches were first used to model pBOO in male mice. One approach involves a retropubic incision to apply and cinch a suture or metal ring around the bladder neck or pelvic urethra to drive bladder compensation and overactive bladder, and later bladder decompensation, detrusor underactivity, fibrosis, and loss of muscle mass [228][229][230][231]. The mouse model has been essential for recognizing new druggable pathways for restoring function to the decompensated bladder [232].…”