Lack of CCM1 induces hypersprouting and impairs response to flow

Tara M Mleynek; Aubrey C Chan; Michael Redd; Christopher C Gibson; Chadwick T Davis; Dallas S Shi; Tiehua Chen; Kandis L Carter; Jing Ling; Raquel Blanco; Holger Gerhardt; Kevin Whitehead; Dean Y Li

doi:10.1093/hmg/ddu342

Back

Lack of CCM1 induces hypersprouting and impairs response to flow

Journal article

Open access

Peer reviewed

Lack of CCM1 induces hypersprouting and impairs response to flow

Tara M Mleynek, Aubrey C Chan, Michael Redd, Christopher C Gibson, Chadwick T Davis, Dallas S Shi, Tiehua Chen, Kandis L Carter, Jing Ling, Raquel Blanco, …

Human molecular genetics, Vol.23(23), pp.6223-6234

12/01/2014

DOI: 10.1093/hmg/ddu342

PMCID: PMC4222362

PMID: 24990152

Files and links (1)

url

https://doi.org/10.1093/hmg/ddu342View

Published (Version of record) Open Access

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.

Animals

Animals, Genetically Modified

Hemangioma, Cavernous, Central Nervous System - genetics

Hemangioma, Cavernous, Central Nervous System - metabolism

Hemangioma, Cavernous, Central Nervous System - pathology

Humans

KRIT1 Protein

Mice, Knockout

Microtubule-Associated Proteins - genetics

Microtubule-Associated Proteins - metabolism

Proto-Oncogene Proteins - genetics

Proto-Oncogene Proteins - metabolism

Retina - pathology

Zebrafish

Details

Title: Subtitle: Lack of CCM1 induces hypersprouting and impairs response to flow
Creators: Tara M Mleynek - University of Utah
Aubrey C Chan - University of Utah
Michael Redd - University of Utah
Christopher C Gibson - University of Utah
Chadwick T Davis - University of Utah
Dallas S Shi - University of Utah
Tiehua Chen - University of Utah
Kandis L Carter - University of Utah
Jing Ling - University of Utah
Raquel Blanco - Cancer Research UK
Holger Gerhardt - KU Leuven
Kevin Whitehead - University of Utah
Dean Y Li - Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.23(23), pp.6223-6234
DOI: 10.1093/hmg/ddu342
PMID: 24990152
PMCID: PMC4222362
NLM abbreviation: Hum Mol Genet
ISSN: 0964-6906
eISSN: 1460-2083
Grant note: R01 NS075168 / NINDS NIH HHS R01HL065648 / NHLBI NIH HHS R01 NS080893 / NINDS NIH HHS
Language: English
Date published: 12/01/2014
Academic Unit: Psychiatry; Internal Medicine
Record Identifier: 9984280833502771

Metrics

24 Record Views

30 Times Cited - Web of Science