Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation
Identifieur interne : 006445 ( Main/Exploration ); précédent : 006444; suivant : 006446Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation
Auteurs : Meredith Downes ; Mathias Franois ; Charles Ferguson [Australie] ; Robert G. Parton [Australie] ; Peter Koopman [Australie]Source :
- Human Molecular Genetics [ 0964-6906 ] ; 2009-08-01.
Descripteurs français
- KwdFr :
- Animaux, Facteurs de transcription SOX-F (génétique), Facteurs de transcription SOX-F (métabolisme), Humains, Hypotrichose (embryologie), Hypotrichose (génétique), Hypotrichose (métabolisme), Hypotrichose (physiopathologie), Lymphoedème (embryologie), Lymphoedème (génétique), Lymphoedème (métabolisme), Lymphoedème (physiopathologie), Modèles animaux de maladie humaine, Mâle, Souris, Souris de lignée DBA, Télangiectasie (embryologie), Télangiectasie (génétique), Télangiectasie (métabolisme), Télangiectasie (physiopathologie), Vaisseaux sanguins (embryologie), Vaisseaux sanguins (malformations), Vaisseaux sanguins (métabolisme), Vaisseaux sanguins (physiopathologie).
- MESH :
- embryologie : Hypotrichose, Lymphoedème, Télangiectasie, Vaisseaux sanguins.
- génétique : Facteurs de transcription SOX-F, Hypotrichose, Lymphoedème, Télangiectasie.
- malformations : Vaisseaux sanguins.
- métabolisme : Facteurs de transcription SOX-F, Hypotrichose, Lymphoedème, Télangiectasie, Vaisseaux sanguins.
- physiopathologie : Hypotrichose, Lymphoedème, Télangiectasie, Vaisseaux sanguins.
- Animaux, Humains, Modèles animaux de maladie humaine, Mâle, Souris, Souris de lignée DBA.
- Pascal (Inist)
- Wicri :
- topic : Génétique.
English descriptors
- KwdEn :
- Animal model, Animals, Blood Vessels (abnormalities), Blood Vessels (embryology), Blood Vessels (metabolism), Blood Vessels (physiopathology), Blood vessel, Disease Models, Animal, Genetics, Hair, Humans, Hypotrichosis, Hypotrichosis (embryology), Hypotrichosis (genetics), Hypotrichosis (metabolism), Hypotrichosis (physiopathology), Lymphedema, Lymphedema (embryology), Lymphedema (genetics), Lymphedema (metabolism), Lymphedema (physiopathology), Male, Mice, Mice, Inbred DBA, Mouse, SOXF Transcription Factors (genetics), SOXF Transcription Factors (metabolism), Syndrome, Telangiectasia, Telangiectasis (embryology), Telangiectasis (genetics), Telangiectasis (metabolism), Telangiectasis (physiopathology).
- MESH :
- chemical , genetics : SOXF Transcription Factors.
- abnormalities : Blood Vessels.
- embryology : Blood Vessels, Hypotrichosis, Lymphedema, Telangiectasis.
- genetics : Hypotrichosis, Lymphedema, Telangiectasis.
- metabolism : Blood Vessels, Hypotrichosis, Lymphedema, SOXF Transcription Factors, Telangiectasis.
- physiopathology : Blood Vessels, Hypotrichosis, Lymphedema, Telangiectasis.
- Animals, Disease Models, Animal, Humans, Male, Mice, Mice, Inbred DBA.
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.
Url:
DOI: 10.1093/hmg/ddp219
Affiliations:
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DBA</term><term>Mouse</term><term>SOXF Transcription Factors (genetics)</term><term>SOXF Transcription Factors (metabolism)</term><term>Syndrome</term><term>Telangiectasia</term><term>Telangiectasis (embryology)</term><term>Telangiectasis (genetics)</term><term>Telangiectasis (metabolism)</term><term>Telangiectasis (physiopathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Facteurs de transcription SOX-F (génétique)</term><term>Facteurs de transcription SOX-F (métabolisme)</term><term>Humains</term><term>Hypotrichose (embryologie)</term><term>Hypotrichose (génétique)</term><term>Hypotrichose (métabolisme)</term><term>Hypotrichose (physiopathologie)</term><term>Lymphoedème (embryologie)</term><term>Lymphoedème (génétique)</term><term>Lymphoedème (métabolisme)</term><term>Lymphoedème (physiopathologie)</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Souris</term><term>Souris de lignée DBA</term><term>Télangiectasie 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type="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.</div></front></TEI><affiliations><list><country><li>Australie</li></country></list><tree><noCountry><name sortKey="Downes, Meredith" sort="Downes, Meredith" uniqKey="Downes M" first="Meredith" last="Downes">Meredith Downes</name><name sortKey="Franois, Mathias" sort="Franois, Mathias" uniqKey="Franois M" first="Mathias" last="Franois">Mathias Franois</name></noCountry><country name="Australie"><noRegion><name sortKey="Ferguson, Charles" sort="Ferguson, Charles" uniqKey="Ferguson C" first="Charles" last="Ferguson">Charles Ferguson</name></noRegion><name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name><name sortKey="Parton, Robert G" sort="Parton, Robert G" uniqKey="Parton R" first="Robert G." last="Parton">Robert G. Parton</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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