Lack of CCM1 induces hypersprouting and impairs response to flow.
Hum Mol Genet
; 23(23): 6223-34, 2014 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-24990152
ABSTRACT
Cerebral cavernous malformation (CCM) is a disease of vascular malformations known to be caused by mutations in one of three genes CCM1, CCM2 or CCM3. Despite several studies, the mechanism of CCM lesion onset remains unclear. Using a Ccm1 knockout mouse model, we studied the morphogenesis of early lesion formation in the retina in order to provide insight into potential mechanisms. We demonstrate that lesions develop in a stereotypic location and pattern, preceded by endothelial hypersprouting as confirmed in a zebrafish model of disease. The vascular defects seen with loss of Ccm1 suggest a defect in endothelial flow response. Taken together, these results suggest new mechanisms of early CCM disease pathogenesis and provide a framework for further study.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retina
/
Proteínas Proto-Oncogênicas
/
Hemangioma Cavernoso do Sistema Nervoso Central
/
Proteínas Associadas aos Microtúbulos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2014
Tipo de documento:
Article