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. 2020 Jul 10;217(10):e20200140. doi: 10.1084/jem.20200140

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© 2020 Hong et al.

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Figure 2. — Endothelial loss of ADAMTS5 reduces CCM formation. (A) Schematic representation of Adamts5 targeting construct and strategy to create Adamts5^fl and Adamts5^RC alleles. RC denotes recombined allele following Cre activity. F1-R1 and F2-R2 represent primers used for screening and detecting recombination. (B) Immunostaining of versican in P6 cerebellums from Krit1^ECKO;Adamts5^+/+, Krit1^ECKO;Adamts5^fl/+, and Krit1^ECKO;Adamts5^fl/fl mice. Boxed regions are shown at higher magnification to the right. Dotted lines delineate white matter. Asterisks indicate erythrocyte autofluorescence. Scale bars, 150 µm. (C) Quantitation of versican IntDen along the white matter tracts relative to Krit1^ECKO;Adamts5^+/+ (n = 6 from three litters, ANOVA + Tukey test). A.U., arbitrary units. (D and E) Genetic rescue of CCM formation with endothelial-specific loss of ADAMTS5. Visual detection of CCM lesions in the hindbrains of P10 littermates (D, top), corresponding composite microCT images (D, bottom), and quantification of CCM lesion volumes (E; n = 8–10 from six litters, ANOVA + Tukey test). Scale bars, 1 mm. Error bars represent ± SEM; *, P < 0.05; **, P < 0.01.