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. 2011 Apr 25;121(5):2048–2059. doi: 10.1172/JCI45636

Figure 6. Attenuation of prolapse phenotypes in Fbln5–/–;Mmp9–/– (DKO) mice.

Figure 6

(A) Postnatal analysis of MMP-9 levels in WT and Fbln5–/– (KO) vaginas. Vaginas were harvested at indicated day and subjected to gelatin zymography. Note an increase in MMP-9 activity in the mutants at 24 days of age but not in WT. PC, adult KO vagina serves as a positive control. In WT gel, first 11 lanes were run on the same gel but were not contiguous. (B) Prolapse development in Fbln5+/+ (n = 16–23, white circles), Fbln5–/–;Mmp9+/+ (n = 25–36, black triangles), Fbln5–/–;Mmp9+/– (n = 39–42, black squares), and DKO (n = 18–25, black circles) from 6–46 weeks. Data represent percentage of animals developing overt prolapse (≥ stage 2). Although prolapse was assessed weekly, for simplicity, data are presented at 4-week intervals. *P < 0.01 compared with Fbln5–/–;Mmp9+/+ or Fbln5–/–;Mmp9+/–, log-rank survival analysis. (C) Representative images of KO (left) and DKO (right) littermates at 33 weeks. Note rescue of urogenital bulge (arrow) and anal prolapse (a) in DKO. (D) Representative Hart’s staining (upper panels) of transverse sections of the mid-vagina from KO (n = 6) or DKO (n = 6) mice at 1 year of age. A marked increase in elastic fiber density is observed in the subepithelial stroma of DKO mice. Pentachrome staining (lower panels) of the vagina from KO (n = 3) or DKO (n = 3) mice at 1 year old. Note collagen fibrils were thicker and continuous in DKO mice compared with Fbln5–/– mice (insets). Scale bars: 20 μm. (E) Quantification of elastic fiber density. (F) Collagen area fraction. Each symbol represents mean determination from a single animal. Data are represented as mean ± SEM. *P < 0.05.