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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Plummer, NW; Squire, TL; Srinivasan, S; Huang, E; Zawistowski, JS; Matsunami, H; Hale, LP; Marchuk, DA

Published Date

  • February 2006

Published In

Volume / Issue

  • 17 / 2

Start / End Page

  • 119 - 128

PubMed ID

  • 16465592

International Standard Serial Number (ISSN)

  • 0938-8990

Digital Object Identifier (DOI)

  • 10.1007/s00335-005-0098-8


  • eng

Conference Location

  • United States