Quantification of pelvic organ prolapse in mice: vaginal protease activity precedes increased MOPQ scores in fibulin 5 knockout mice.
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.
Wieslander
Cecilia K
CK
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.
Rahn
David D
DD
McIntire
Donald D
DD
Acevedo
Jesús F
JF
Drewes
Peter G
PG
Yanagisawa
Hiromi
H
Word
R Ann
RA
D000375:Aging / Q000378:metabolism; D000818:Animals; D004547:Elastic Tissue / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D015588:Observer Variation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D014596:Uterine Prolapse / Q000378:metabolism* / Q000503:physiopathology; D014621:Vagina / Q000378:metabolism* / Q000503:physiopathology
D016326:Extracellular Matrix Proteins; C120769:Fbln5 protein, mouse; D011994:Recombinant Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9