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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/F545    most recent 00063.2008v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lee, U. J. Articles by Damaser, M. S. Search for Related Content PubMed PubMed Citation Articles by Lee, U. J. Articles by Damaser, M. S.

Lower urogenital tract anatomical and functional phenotype in lysyl oxidase like-1 knockout mice resembles female pelvic floor dysfunction in humans

¹Glickman Urological and Kidney Institute, ²Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, and ³Department of Biomedical Engineering, Cleveland Clinic, Cleveland; ⁴Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland; ⁵Department of Radiology, Case Western Reserve University, Cleveland, Ohio; and ⁶Department of Ophthalmology (Neuroscience), Massachusetts Eye and Ear Infirmary, Boston, Massachusetts

Submitted 16 February 2008 ; accepted in final form 15 May 2008

Female pelvic floor dysfunction (FPFD) is a complex group of conditions that include urinary incontinence and pelvic organ prolapse (POP). In humans, elastin homeostasis has been implicated in the pathophysiology of FPFD. Lysyl oxidase-like 1 knockout (LOXL1-KO) mice demonstrate abnormal elastic fiber homeostasis and develop FPFD after parturition. We compared the lower urogenital tract (LUT) anatomy and function in LOXL1-KO mice with and without POP. LUT anatomy was assessed in LOXL1-KO mice over 28 wk. Pelvic visceral anatomy in LOXL1-KO was evaluated with a 7-Tesla magnetic resonance imaging (MRI) scanner. LUT function was assessed using conscious cystometry and leak point pressure (LPP) testing. Quantitative histological analysis of elastic fibers was performed on external urethral sphincter (EUS) cross sections. By 25 wk of age, 50% of parous LOXL1-KO mice developed POP. LOXL1-KO mice with POP had greater variability in the size and location of the bladder on MRI compared with mice without POP. Parity and POP were associated with lower LPP. Elastin clusters were significantly increased in the EUS of LOXL1-KO mice with POP. Because parity triggers POP in LOXL1-KO mice, LOXL1-KO mice with POP have variable internal pelvic anatomy, and both parity and POP are associated with a decrease in LPP, we conclude that LOXL1 LUT anatomical and functional phenotype resembles FPFD in humans. The increase in elastin clusters in the urethra of LOXL1-KO mice with POP suggests that elastin disorganization may lead to functional abnormalities. We conclude that LOXL1 warrants further investigation in the pathphysiology of FPFD.

lysyl oxidase-like 1 knockout; elastin; pelvic organ prolapse; urinary incontinence; urodynamics