Lack of CCM1 induces hypersprouting and impairs response to flow

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Item Type:	Article
Title:	Lack of CCM1 induces hypersprouting and impairs response to flow
Creators Name:	Mleynek, T.M., Chan, A.C., Redd, M., Gibson, C.C., Davis, C.T., Shi, D.S., Chen, T., Carter, K.L., Ling, J., Blanco, R., Gerhardt, H., Whitehead, K. and Li, D.Y.
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.
Keywords:	Central Nervous System Cavernous Hemangioma, Genetically Modified Animals, KRIT1 Protein, Knockout Mice, Microtubule-Associated Proteins, Proto-Oncogene Proteins, Retina, Animals, Mice, Zebrafish
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	23
Number:	23
Page Range:	6223-6234
Date:	1 December 2014
Official Publication:	https://doi.org/10.1093/hmg/ddu342
PubMed:	View item in PubMed

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