Fig. 2.
The slow progression model of cerebral cavernous malformation (CCM) develops large lesions. A chronic model of CCM was generated by treating Cdh5(PAC)-Cre-ERT2/Ccm3f/f/R26R-Confetti mice with low-dose tamoxifen. a Scheme of treatment with tamoxifen at P2 and analysis at P8, P14 and P30. b Representative photographs of whole brains from chronic P8, P14 and P30 mice; scale bar: 100 μm. c Representative tiling of a cerebellum at P14 showing the distribution of lesions; upper panel shows a projection from a 1-mm-thick section; lower panels show three-dimensional reconstruction of corresponding regions. Lower left panel was rotated by 90°; vessels were stained for Podocalyxin; scale bars: 1000 μm lower magnification, 300 μm higher magnification. d Representative confocal image of P30 retina stained for Isolectin B4 (black vessels) showing large cavernomas at the front; scale bar: 500 μm lower magnification, 100 μm higher magnification. e Representative confocal images of P30 brain stained for Isolectin B4 (black vessels) showing cavernomas in the hippocampus and the olfactory bulb; 1000 μm lower magnification, 500 μm higher magnification. f, g Quantification of total number and mean area of lesions in chronic P8, P14 and P30 mice. Data are means ± SE; p < 0.001 among groups (one-way analysis of variance (ANOVA)); *p < 0.01 (Tukey’s post hoc test). h Lesions were divided into four groups according to their size, as shown. Data are means ± SE. *p < 0.001 among groups (one-way ANOVA); p < 0.01 (Tukey’s post hoc test); a total of 1698 lesions have been counted from 5 animals at P7, 4 animals at P14 and 9 at P30. Source data are provided as a Source Data file