While mouse models have provided invaluable insights into key mechanisms of CCM pathogenesis, e.g., deregulation of MEKK3-KLF2/4 signaling, increased endothelial activation of PI3K-mTOR signaling, loss of junctional integrity, clonal expansion of KO ECs, or recruitment of WT cells into growing CCM lesions [17, 31, 32, 65–68], they can hardly be used for a comprehensive comparison between CCM1, CCM2, and CCM3 KO conditions. This evidence concerns the gene MAP3K3 and cerebral cavernous malformation.