PUBLICATION
Lack of CCM1 Induces Hypersprouting and Impairs Response to Flow
- Authors
- Mleynek, T.M., Chan, A., Redd, M., Gibson, C.C., Davis, C., Shi, D.S., Chen, T., Carter, K.L., Ling, J., Blanco, R., Gerhardt, H., Whitehead, K., Li, D.Y.
- ID
- ZDB-PUB-140706-14
- Date
- 2014
- Source
- Human molecular genetics 23(23): 6223-34 (Journal)
- Registered Authors
- Redd, Michael
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Hemangioma, Cavernous, Central Nervous System/genetics
- Hemangioma, Cavernous, Central Nervous System/metabolism
- Hemangioma, Cavernous, Central Nervous System/pathology*
- Humans
- Mice, Knockout
- Microtubule-Associated Proteins/genetics*
- Microtubule-Associated Proteins/metabolism
- Proto-Oncogene Proteins/genetics*
- Proto-Oncogene Proteins/metabolism
- Retina/pathology*
- Zebrafish
- PubMed
- 24990152 Full text @ Hum. Mol. Genet.
Citation
Mleynek, T.M., Chan, A., Redd, M., Gibson, C.C., Davis, C., Shi, D.S., Chen, T., Carter, K.L., Ling, J., Blanco, R., Gerhardt, H., Whitehead, K., Li, D.Y. (2014) Lack of CCM1 Induces Hypersprouting and Impairs Response to Flow. Human molecular genetics. 23(23):6223-34.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping