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Mouse Knockout Models for Pelvic Organ Prolapse: a Systematic Review

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Abstract

Introduction and hypothesis

Mouse knockout (KO) models of pelvic organ prolapse (POP) have contributed mechanistic evidence for the role of connective tissue defects, specifically impaired elastic matrix remodeling. Our objective was to summarize what mouse KO models for POP are available and what have we learned from these mouse models about the pathophysiological mechanisms of POP development.

Methods

We conducted a systematic review and reported narrative findings according to PRISMA guidelines. Two independent reviewers searched PubMed, Scopus and Embase for relevant manuscripts and conference abstracts for the time frame of January 1, 2000, to March 31, 2021. Conference abstracts were limited to the past 5 years.

Results

The search strategy resulted in 294 total titles. We ultimately included 25 articles and an additional 11 conference abstracts. Five KO models have been studied: Loxl1, Fbln5, Fbln3, Hoxa11 and Upii-sv40t. Loxl1 and Fbln5 KO models have provided the most reliable and predictable POP phenotype. Loxl1 KO mice develop POP primarily from failure to heal after giving birth, whereas Fbln5 KO mice develop POP with aging. These mouse KO models have been used for a wide variety of investigations including genetic pathways involved in development of POP, biomechanical properties of the pelvic floor, elastic fiber deposition, POP therapies and the pathophysiology associated with mesh complications.

Conclusions

Mouse KO models have proved to be a valuable tool in the study of specific genes and their role in the development and progression of POP. They may be useful to study POP treatments and POP complications.

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Acknowledgements

We thank Mr. Fábio Lage for his assistance in creating the Figure 1 illustration.

Funding

This work supported by NIH grants R21HD095234, R21HD095521, Cleveland Clinic and the Rehabilitation Research and Development Service of the Department of Veterans Affairs (Margot S. Damaser).

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Authors and Affiliations

  1. Department of Internal Medicine, University of Utah, Williams Building 295 Chipeta Way, Salt Lake City, UT, USA

    Kristina Allen-Brady

  2. Department of Gynecology, Sector of Urogynecology, Universidade Federal de São Paulo, São Paulo, Brazil

    Maria A. T. Bortolini

  3. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Margot S. Damaser

  4. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA

    Margot S. Damaser

  5. Advanced Platform Technology Center, Louis Stokes Department of Veterans Affairs Medical Center, Cleveland, OH, USA

    Margot S. Damaser

Authors
  1. Kristina Allen-Brady
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  2. Maria A. T. Bortolini
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  3. Margot S. Damaser
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Contributions

K Allen-Brady: project development, literature review, manuscript writing/editing.

MAT Bortolini: project development, literature review, manuscript writing/editing.

MS Damaser: project development, literature review, manuscript writing/editing.

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Correspondence to Kristina Allen-Brady.

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Allen-Brady, K., Bortolini, M.A.T. & Damaser, M.S. Mouse Knockout Models for Pelvic Organ Prolapse: a Systematic Review. Int Urogynecol J 33, 1765–1788 (2022). https://doi.org/10.1007/s00192-021-05066-5

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  • DOI: https://doi.org/10.1007/s00192-021-05066-5

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