Validation of genetically matched wild-type strain and lysyl oxidase-like 1 knockout mouse model of pelvic organ prolapse.

Abstract

OBJECTIVES:

Lysyl oxidase-like 1 knockout (Loxl1) mice demonstrate deficient elastin homeostasis associated with pelvic organ prolapse (POP). To further investigate the pathophysiology of POP in these animals, a genetically matched homozygous positive (Loxl1) or wild-type strain is needed. This study sought to create and validate genetically matched Loxl1 and Loxl1 strains.

METHODS:

Female Loxl1 mice were backcrossed with male wild-type mice. The resultant heterozygous mice were bred to produce Loxl1 and Loxl1 mice, whose genotype was confirmed by polymerase chain reaction (PCR). Multiparous female Loxl1 (n = 7) and Loxl1 (n = 9) mice were assessed for POP weekly for 12 weeks after their first vaginal delivery. Pelvic organ prolapse was compared between groups using a Kaplan-Meier survival curve with P of less than 0.05 indicating a significant difference. Vaginal connective tissue histologic finding was assessed qualitatively and quantitatively.

RESULTS:

There were no significant differences between the groups in age or parity. Of the 7 Loxl1 mice, 4 developed prolapse by 8 weeks and 6 by 12 weeks postpartum. No Loxl1 mouse prolapsed. Loxl1 mice had significantly larger vaginas as determined by area within the lumen and total cross-sectional tissue area. Striated muscle fibers of the urethra in Loxl1 mice were less organized, shorter, and thinner than in Loxl1 mice.

CONCLUSIONS:

Genetically matched Loxl1 and Loxl1 strains can be reliably created by a backcross method and differentiate in their prolapse phenotype. Loxl1 mice demonstrate pathology primarily characterized by enlargement of the vagina. Further studies are needed to elucidate the cause of this finding.

• Authors: Bruna M Couri, Ali Borazjani, Andrew T Lenis, Brian Balog, Mei Kuang, Dan Li Lin, Margot S Damaser
• Journal: Female pelvic medicine & reconstructive surgery (Female Pelvic Med Reconstr Surg) 2014 Sep-Oct Vol. 20 Issue 5 Pg. 287-92 ISSN: 2154-4212 [Electronic] United States
• PMID: 25181380 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amino Acid Oxidoreductases
• Loxl1 protein, mouse

Topics

• Amino Acid Oxidoreductases (genetics)
• Animals
• Disease Models, Animal
• Female
• Mice
• Mice, Knockout
• Pelvic Organ Prolapse (genetics, pathology)
• Postpartum Period
• Reproducibility of Results
• Vagina (pathology)