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Lack of CCM1 induces hypersprouting and impairs response to flow

Item Type:Article
Title:Lack of CCM1 induces hypersprouting and impairs response to flow
Creators Name:Mleynek, T.M. and Chan, A.C. and Redd, M. and Gibson, C.C. and Davis, C.T. and Shi, D.S. and Chen, T. and Carter, K.L. and Ling, J. and Blanco, R. and Gerhardt, H. and 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 (U.K.)
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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