Wieslander Cecilia K, Rahn David D, McIntire Donald D, Acevedo Jesús F, Drewes Peter G, Yanagisawa Hiromi, Word R Ann
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.
Biol Reprod. 2009 Mar;80(3):407-14. doi: 10.1095/biolreprod.108.072900. Epub 2008 Nov 5.
Two mouse models of pelvic organ prolapse have been generated recently, both of which have null mutations in genes involved in elastic fiber synthesis and assembly (fibulin 5 and lysyl oxidase-like 1). Interestingly, although these mice exhibit elastinopathies early in life, pelvic organ prolapse does not develop until later in life. In this investigation we developed and validated a tool to quantify the severity of pelvic organ prolapse in mice, and we used this tool prospectively to study the role of fibulin 5, aging, and vaginal proteases in the development of pelvic organ prolapse. The results indicate that >90% of Fbln5(-/-) mice develop prolapse by 6 mo of age, even in the absence of vaginal delivery, and that increased vaginal protease activity precedes the development of prolapse.
最近已构建出两种盆腔器官脱垂的小鼠模型,这两种模型在参与弹性纤维合成和组装的基因(纤连蛋白5和赖氨酰氧化酶样1)中存在无效突变。有趣的是,尽管这些小鼠在生命早期就表现出弹性纤维病,但盆腔器官脱垂直到生命后期才会出现。在本研究中,我们开发并验证了一种用于量化小鼠盆腔器官脱垂严重程度的工具,并前瞻性地使用该工具研究纤连蛋白5、衰老和阴道蛋白酶在盆腔器官脱垂发生过程中的作用。结果表明,即使在没有阴道分娩的情况下,超过90%的Fbln5(-/-)小鼠在6月龄时会发生脱垂,并且阴道蛋白酶活性增加先于脱垂的发生。