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

[lymphedemapeople]

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

Hum Mol Genet. 2009 May

Downes M, François M, Ferguson C, Parton RG, Koopman P.
Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.

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 (Ra(Op)).
Early genesis and patterning of vasculature was unimpaired in Ra(Op)
embryos, but surface capillaries became enlarged from 12.5 dpc and
embryos developed massive surface haemorrhage 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 Ra(Op)
embryos, suggesting 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.

Oxford Journal

http://hmg.oxfordjournals.org/cgi/content/abstract/ddp219v1