Fig. 2. Dilated cranial vessels in Ccm1^-/- mice phenocopy human cavernous malformations. (A-D) Immunohistochemical staining for the endothelial antigen Pecam on cross-sections from cranial portions of the embryo. (A,B) Immunostaining reveals the plexus of head vessels at E8.5. Significant enlargement of cranial vessels is observed early in Ccm1^-/- embryos (B). (C,D) Examination of embryos at E9.5 shows further enlargement of cranial vessels in Ccm1^-/- embryos, which now occupy much of the region normally encompassed by mesenchymal tissue. By this stage, Ccm1^-/- mice are readily distinguished from their phenotypically normal littermates and no further embryonic enlargement is observed. (E,F) Comparison of a human cavernous malformation (E) with a similar magnification of a Ccm1^-/- mouse embryo (F) shows cavernous vascular channels surrounded by a thin layer of Pecam-stained endothelium (stained brown). Human lesions contain vessels of widely varying sizes, some larger than those shown. Scale bars: 100 µm.