Figure 10. FEVR-like phenotypes in double-heterozygous deletion of Ctnnd1 and Ctnna1 or Ctnnb1 in mouse ECs and schematic diagram of the mechanism for p120 deficiency in the pathogenesis of FEVR.

(A) Representative immunofluorescence images of P5 Ctrl, Ctnnd1^iECKO/+, and Ctnnd1^iECKO/+ Ctnnb1^iECKO/+ mouse retinas labeled with IB4 (green) and Ter119 (red). The white arrows indicate abnormal leakage of erythrocytes. Scale bars, 200 μm. (B) Representative immunofluorescence images of P7 Ctrl, Ctnnd1^iECKO/+, and Ctnnd1^iECKO/+ Ctnna1^iECKO/+ mouse retinas labeled with IB4 (green) and Ter119 (red). The white arrows and dotted region indicate abnormal leakage of erythrocytes. Scale bars, 200 μm. (C) Quantification of vascular progression of P5 Ctrl, Ctnnd1^iECKO/+, and Ctnnd1^iECKO/+ Ctnnb1^iECKO/+ mouse retinas. Error bars, SDs. The P values are from multiple comparisons in 1-way ANOVA with Dunnett’s multiple comparisons tests (n = 6); ****P < 0.0001. (D) Quantification of vascular progression of P7 Ctrl, Ctnnd1^iECKO/+, and Ctnnd1^iECKO/+ Ctnna1^iECKO/+ mouse retinas. Error bars, SDs. The P values are from multiple comparisons in 1-way ANOVA with Dunnett’s multiple comparisons tests (n = 6); ***P < 0.001. (E) Inactivation of Wnt signaling (upper panel) and disruption of AJs (lower panel) lead to similar but distinct retinal vascular defects. Deficient p120 function causes FEVR through combined effects of Wnt inactivation and AJ disruption (right panel). Inactivation of Wnt signaling contributes to i) delayed vascular progression, ii) decreased inner vessel density, iii) artery/vein intersection, iv) hyperplasia of peripheral vasculature, and v) moderate vascular leakage (upper panel). Disruption of AJs contributes to i) extensive vascular leakage and ii) vascular hyperplasia (lower panel). Experiments were performed at least 3 times independently.