Una Lee, MD, Firouz Daneshgari, MD, Guiming Liu, MD, Mei Li, MD, PhD, Dan Li Lin, MD, Paul Zaszczurynski, Hui Q. Pan, MD, PhD, Tiansen Li, PhD, Margot S. Damaser, PhD

Cleveland Clinic Foundation, Cleveland, OH; Louis Stokes Cleveland VA Medical Center, Cleveland, OH; Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA

Objectives: Using a Loxl1^–/– genetic knockout mouse model, we have previously shown that genetic deficiency of LOXL1, a lysyl oxidase-like enzyme which can polymerize elastin, results in pelvic organ prolapse and increased voiding frequency postpartum. The objective of this study was to determine if Loxl1^–/– mutant mice demonstrate either urinary incontinence or decreased urethral resistance.

Methods: Female parous Loxl1^–/– mice (n=5), in the stable postpartum period with pelvic organ descent, as well as age-matched female wild type (WT) mice (n=6) underwent conscious cystometry, measurement of residual urine, and leak point pressure (LPP) testing. After completion of testing, bladders were removed and muscle strips were used for contractility studies. Strips were stimulated by varying levels of KCl, electrical fields (EFS), adenosine 5’- triphosphate (ATP), and carbachol (CCh).

Results: There are no significant differences between the weights of the bladder. Loxl1^–/– mice void more frequently during cystometry testing than WT mice, consistent with previous work demonstrating increased frequency in these mice. Loxl1^–/– mice had a decreased micturition pressure during cystometry than WT mice. Residual urine was not significantly different between WT and Loxl1^–/– mice, indicating that the urinary frequency is not a result of outlet obstruction. LPP was not significantly different between WT and Loxl1^–/– mice. However, the volume at which LPP was measured was significantly lower in Loxl1^–/– mice than WT mice, due to their frequency of voids. In addition, there are no significant differences between the responses of bladder strips from Loxl1^–/– mice and WT mice in the responsiveness to various stimulus.

Conclusion: Loxl1^–/– mutant mice in the stable phase of prolapse do not have decreased urethral resistance with limited bladder capacity. Confirmation of presence of urinary incontinence in view of previously observed increased frequency of voids in these mutant mice warrants further investigation into the function of lower urinary tract of the animals.

Supported by NIH grant -KO8 DK02631 and Animal Models of Diabetic Complications Consortium (www.amdcc.org) grant DK61018-02S1

UroToday.com Coverage of SUFU 2007

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