Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation

Downes, Meredith, Francois, Mathias, Ferguson, Charles, Parton, Robert G. and Koopman, Peter (2009) Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation. Human Molecular Genetics, 18 15: 2839-2850. doi:10.1093/hmg/ddp219


Author Downes, Meredith
Francois, Mathias
Ferguson, Charles
Parton, Robert G.
Koopman, Peter
Title Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2009-08-01
Year available 2009
Sub-type Article (original research)
DOI 10.1093/hmg/ddp219
Open Access Status Not Open Access
Volume 18
Issue 15
Start page 2839
End page 2850
Total pages 12
Editor Kay Davies
Anthony Wynshaw-Boris
Joel Hirschhorn
Place of publication Oxford, England, U. K.
Publisher Oxford University Press
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060403 Developmental Genetics (incl. Sex Determination)
Abstract Mutations in the transcription factor gene SOX18 cause vascular, lymphatic and hair follicle defects in humans with dominant and recessive forms of hypotrichosis-lymphedema-telangiectasia (HLT) syndrome. Here, we clarify the role of SOX18 in the vascular dysfunction in HLT by ultrastructural, immunofluorescence, molecular and functional analysis of vascular anomalies in embryos of the naturally occurring Sox18-mutant mouse strain ragged-opossum (RaOp). Early genesis and patterning of vasculature was unimpaired in RaOp embryos, but surface capillaries became enlarged from 12.5 dpc and embryos developed massive surface hemorrhage by 14.5 dpc. Large focal breaches in the endothelial barrier were observed, in addition to endothelial hyperplasia associated with impaired pericyte recruitment to the microvasculature. Expression of the genes encoding the endothelial factors MMP7, IL7R and N-cadherin was reduced in RaOp embryos, suggesting that these are downstream targets of SOX18. Together, our results indicate that vascular anomalies in HLT arise from defects in regulation of genes required for the acquisition of structural integrity during microvascular maturation.
Keyword Endothelial growth factor
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID BB/C520712/1
BBS/E/B/0000M221
G0700740
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 03 Sep 2009, 17:51:05 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience