Skip to main content
Top
Published in: International Urogynecology Journal 1/2009

01-01-2009 | Original Article

Inherited pelvic organ prolapse in the mouse: preliminary evaluation of a new murine model

Authors: Anna R. McNanley, Aimee M. Johnson, Michael K. Flynn, Ronald W. Wood, Scott D. Kennedy, Jay E. Reeder

Published in: International Urogynecology Journal | Issue 1/2009

Login to get access

Abstract

The objective of this study was to report the initial anatomic, radiographic, and genetic evaluations of a novel form of spontaneous pelvic organ prolapse (S-POP) in mice. We observed S-POP in a colony of UPII-SV40T transgenic mice developed for studies on bladder cancer. We utilized magnetic resonance imaging and necropsy to characterize this finding. We have established a breeding colony to identify inheritance patterns and for future studies. Selective breeding isolated the S-POP phenotype from the transgene. In contrast to other animal models, the S-POP mouse does not require an obligatory antecedent event to manifest pelvic organ prolapse. Necropsy and imaging demonstrate significant displacement of the pelvic organs distal to the pelvic floor in both sexes. The appearance of the POP is similar to that seen in the human female phenotype. Preliminary breeding studies indicate an autosomal dominant inheritance pattern. This mouse may be an effective animal model for the study of POP in humans.
Literature
1.
go back to reference Bump RC, Norton PA (1998) Epidemiology and natural history of pelvic floor dysfunction. Obstet Gynecol Clin North Am 25:723–746PubMedCrossRef Bump RC, Norton PA (1998) Epidemiology and natural history of pelvic floor dysfunction. Obstet Gynecol Clin North Am 25:723–746PubMedCrossRef
2.
go back to reference Subak LL, Waetjen LE, van den Eeden S (2001) Cost of pelvic organ prolapse surgery in the United States. Obstet Gynecol 98:646–661PubMedCrossRef Subak LL, Waetjen LE, van den Eeden S (2001) Cost of pelvic organ prolapse surgery in the United States. Obstet Gynecol 98:646–661PubMedCrossRef
3.
go back to reference Buchsbaum GM, Duecy EE, Kerr LA et al (2005) Urinary incontinence in nulliparous women and their parous sisters. Obstet Gynecol 106:1253–1258PubMed Buchsbaum GM, Duecy EE, Kerr LA et al (2005) Urinary incontinence in nulliparous women and their parous sisters. Obstet Gynecol 106:1253–1258PubMed
4.
go back to reference Jack GS, Nikolova G, Vilain E (2005) Familial transmission of genitovaginal prolapse. Int Urogynecol J Pelvic Floor Dysfunct 20:1–4 Jack GS, Nikolova G, Vilain E (2005) Familial transmission of genitovaginal prolapse. Int Urogynecol J Pelvic Floor Dysfunct 20:1–4
5.
go back to reference Kim S, Harvey MA, Johnston S (2005) A review of the epidemiology and pathophysiology of pelvic floor dysfunction: do racial differences matter. J Obstet Gynecol 27:251–259 Kim S, Harvey MA, Johnston S (2005) A review of the epidemiology and pathophysiology of pelvic floor dysfunction: do racial differences matter. J Obstet Gynecol 27:251–259
6.
go back to reference Dietz HP (2003) Do Asian women have less pelvic organ mobility than Caucasians? Int Urogynecol J Pelvic Floor Dysfunct 14:250–253PubMedCrossRef Dietz HP (2003) Do Asian women have less pelvic organ mobility than Caucasians? Int Urogynecol J Pelvic Floor Dysfunct 14:250–253PubMedCrossRef
7.
go back to reference Nikolova G, Lee H, Berkovitz S et al (2007) Sequence variant in the laminin γ1 (LAMC1) gene associated with familial pelvic organ prolapse. Hum Genet 120:847–856PubMedCrossRef Nikolova G, Lee H, Berkovitz S et al (2007) Sequence variant in the laminin γ1 (LAMC1) gene associated with familial pelvic organ prolapse. Hum Genet 120:847–856PubMedCrossRef
8.
go back to reference Visco AG, Yuan L (2003) Differential gene expression in pubococcygeus muscle from patients with pelvic organ prolapse. Am J Obstet Gynecol 189:102–112PubMedCrossRef Visco AG, Yuan L (2003) Differential gene expression in pubococcygeus muscle from patients with pelvic organ prolapse. Am J Obstet Gynecol 189:102–112PubMedCrossRef
9.
go back to reference Kramer L, Gendron J, Pierce L et al (2006) Magnetic resonance imaging of the levator ani in the squirrel monkey: a comparison of muscle volume between a cohort with pelvic organ prolapse and matched normals. Am J Obstet Gynecol 194:1467–1471PubMedCrossRef Kramer L, Gendron J, Pierce L et al (2006) Magnetic resonance imaging of the levator ani in the squirrel monkey: a comparison of muscle volume between a cohort with pelvic organ prolapse and matched normals. Am J Obstet Gynecol 194:1467–1471PubMedCrossRef
10.
go back to reference Mattson J, Kuehl T, Yandell P et al (2005) Evaluation of the aged female baboon as a model of pelvic organ prolapse and pelvic reconstructive surgery. Am J Obstet Gynecol 192:1395–1398PubMedCrossRef Mattson J, Kuehl T, Yandell P et al (2005) Evaluation of the aged female baboon as a model of pelvic organ prolapse and pelvic reconstructive surgery. Am J Obstet Gynecol 192:1395–1398PubMedCrossRef
11.
go back to reference Zhang ZT, Pak J, Shapiro E, Sun TT, Wu XR (1999) Urothelium-specific expression of an oncogene in transgenic mice induced carcinoma in situ and invasive transitional cell carcinoma. Cancer Res 59:3512–3517PubMed Zhang ZT, Pak J, Shapiro E, Sun TT, Wu XR (1999) Urothelium-specific expression of an oncogene in transgenic mice induced carcinoma in situ and invasive transitional cell carcinoma. Cancer Res 59:3512–3517PubMed
12.
go back to reference Johnson AM, Conover DL, Huang J, Messing EM, Ning R, O’Connell MJ, Rossi MA, Sun TT, Wood RW, Wu XR, Reeder JE (2006) Early detection and measurement of urothelial tumors in mice. Urology 67:1309–1314PubMedCrossRef Johnson AM, Conover DL, Huang J, Messing EM, Ning R, O’Connell MJ, Rossi MA, Sun TT, Wood RW, Wu XR, Reeder JE (2006) Early detection and measurement of urothelial tumors in mice. Urology 67:1309–1314PubMedCrossRef
13.
go back to reference Weber AM, Buchsbaum GM, Chen B (2004) Basic science and translational research in female pelvic floor disorders: proceedings of an NIH-sponsored meeting. Neurourol Urodyn 23:288–301PubMedCrossRef Weber AM, Buchsbaum GM, Chen B (2004) Basic science and translational research in female pelvic floor disorders: proceedings of an NIH-sponsored meeting. Neurourol Urodyn 23:288–301PubMedCrossRef
14.
go back to reference Birch C, Fynes MM (2002) The role of synthetic and biologic prostheses in reconstructive pelvic floor surgery. Curr Opin Obstet Gynecol 14:527–535PubMedCrossRef Birch C, Fynes MM (2002) The role of synthetic and biologic prostheses in reconstructive pelvic floor surgery. Curr Opin Obstet Gynecol 14:527–535PubMedCrossRef
15.
go back to reference Liu X, Zhao Y, Gao J et al (2004) Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nat Genet 36:178–182PubMedCrossRef Liu X, Zhao Y, Gao J et al (2004) Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nat Genet 36:178–182PubMedCrossRef
16.
go back to reference Drewes PG, Yanagisawa H, Starcher B et al (2007) Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. Am J Pathol 170:578–589PubMedCrossRef Drewes PG, Yanagisawa H, Starcher B et al (2007) Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. Am J Pathol 170:578–589PubMedCrossRef
17.
go back to reference Xiaoqing L, Zhao Y, Pawlyk B (2006) Failure of elastic fiber homeostasis leads to pelvic floor disorders. Am J Pathol 168:519–527CrossRef Xiaoqing L, Zhao Y, Pawlyk B (2006) Failure of elastic fiber homeostasis leads to pelvic floor disorders. Am J Pathol 168:519–527CrossRef
18.
go back to reference Connell K, Guess M, Chen H et al (2008) HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse. J Clin Invest 118:1050–1055PubMed Connell K, Guess M, Chen H et al (2008) HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse. J Clin Invest 118:1050–1055PubMed
Metadata
Title
Inherited pelvic organ prolapse in the mouse: preliminary evaluation of a new murine model
Authors
Anna R. McNanley
Aimee M. Johnson
Michael K. Flynn
Ronald W. Wood
Scott D. Kennedy
Jay E. Reeder
Publication date
01-01-2009
Publisher
Springer-Verlag
Published in
International Urogynecology Journal / Issue 1/2009
Print ISSN: 0937-3462
Electronic ISSN: 1433-3023
DOI
https://doi.org/10.1007/s00192-008-0723-7

Other articles of this Issue 1/2009

International Urogynecology Journal 1/2009 Go to the issue