Accordingly, whereas mice with the constitutive homozygous knockout of KRIT1 die during early embryogenesis (E9.5) due to extensive cardiovascular defects [35], there is now clear evidence that the inducible, endothelial-specific homozygous knockout of KRIT1 in postnatal mice is not fully sufficient to cause pathological vascular phenotypes underlying CCM disease, suggesting the necessary contribution of additional determinants other than disease-predisposing KRIT1 mutations, including microenvironmental stress events and interindividual variability in stress responses [4,36,37,38]. Here, KRIT1 is linked to cerebral cavernous malformation.