Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations.
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.
Plummer
Nicholas W
NW
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Squire
Teresa L
TL
Srinivasan
Sudha
S
Huang
Elizabeth
E
Zawistowski
Jon S
JS
Matsunami
Hiroaki
H
Hale
Laura P
LP
Marchuk
Douglas A
DA
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D020785:Central Nervous System Vascular Malformations / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000473:pathology; D002831:Choroid Plexus / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D006579:Heterozygote; D017403:In Situ Hybridization; D051379:Mice; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity
D008840:Microfilament Proteins; C480498:osmosensing scaffold for MEKK3 protein, mouse