Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations

Mamm Genome. 2006 Feb;17(2):119-28. doi: 10.1007/s00335-005-0098-8. Epub 2006 Feb 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Brain / blood supply*
  • Brain / metabolism
  • Central Nervous System Vascular Malformations / complications
  • Central Nervous System Vascular Malformations / genetics*
  • Central Nervous System Vascular Malformations / metabolism
  • Cerebral Hemorrhage / etiology
  • Cerebral Hemorrhage / pathology
  • Choroid Plexus / metabolism
  • Disease Models, Animal
  • Endothelium, Vascular / metabolism
  • Heterozygote
  • In Situ Hybridization
  • Mice
  • Microfilament Proteins / biosynthesis
  • Microfilament Proteins / genetics*
  • Molecular Sequence Data
  • Mutation
  • Neurons / metabolism*
  • Organ Specificity


  • Microfilament Proteins
  • osmosensing scaffold for MEKK3 protein, mouse