Cerebral cavernous malformations are vascular defects of the central nervous 
system consisting of clusters of dilated vessels that are subject to frequent 
hemorrhaging. The genes mutated in three forms of autosomal dominant cerebral 
cavernous malformations have been cloned, but it remains unclear which cell type 
is ultimately responsible for the lesion. In this article we describe mice with 
a gene trap insertion in the Ccm2 gene. Consistent with the human phenotype, 
heterozygous animals develop cerebral vascular malformations, although 
penetrance is low. Beta-galactosidase activity in heterozygous brain and in situ 
hybridization in wild-type brain revealed Ccm2 expression in neurons and choroid 
plexus but not in vascular endothelium of small vessels in the brain. The 
expression pattern of Ccm2 is similar to that of the Ccm1 gene and its 
interacting protein ICAP1 (Itgb1bp1). These data suggest that cerebral cavernous 
malformations arise as a result of defects in the neural parenchyma surrounding 
the vascular endothelial cells in the brain.