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

objectivesLysyl 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.

methodsFemale 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.

resultsThere 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.

conclusionsGenetically 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.