PUBLICATION

Arap3 is dysregulated in a mouse model of hypotrichosis-lymphedema-telangiectasia and regulates lymphatic vascular development

Authors
Kartopawiro, J., Bower, N.I., Karnezis, T., Kazenwadel, J., Betterman, K.L., Lesieur, E., Koltowska, K., Astin, J., Crosier, P., Vermeren, S., Achen, M.G., Stacker, S.A., Smith, K.A., Harvey, N.L., François, M., and Hogan, B.M.
ID
ZDB-PUB-131121-24
Date
2014
Source
Human molecular genetics   23(5): 1286-97 (Journal)
Registered Authors
Crosier, Phil, Hogan, Ben M., Kartopawiro, Joelle, Smith, Kelly
Keywords
none
MeSH Terms
  • Syndrome
  • Lymphedema/genetics*
  • GTPase-Activating Proteins/genetics*
  • GTPase-Activating Proteins/metabolism
  • Lymphangiogenesis/genetics*
  • Gene Expression Regulation*
  • Hypotrichosis/genetics*
  • Cell Movement/genetics
  • Female
  • Lymphatic Vessels/metabolism
  • SOXF Transcription Factors/genetics
  • SOXF Transcription Factors/metabolism
  • Adaptor Proteins, Signal Transducing/genetics*
  • Adaptor Proteins, Signal Transducing/metabolism
  • Animals
  • Endothelial Cells/metabolism
  • Mice
  • Vascular Endothelial Growth Factor C/genetics
  • Vascular Endothelial Growth Factor C/metabolism
  • Disease Models, Animal
  • Telangiectasis/genetics*
  • Zebrafish
  • Mice, Knockout
(all 23)
PubMed
24163130 Full text @ Hum. Mol. Genet.
Abstract

Mutations in SOX18, VEGFC and Vascular Endothelial Growth Factor 3 underlie the hereditary lymphatic disorders hypotrichosis–lymphedema–telangiectasia (HLT), Milroy-like lymphedema and Milroy disease, respectively. Genes responsible for hereditary lymphedema are key regulators of lymphatic vascular development in the embryo. To identify novel modulators of lymphangiogenesis, we used a mouse model of HLT (Ragged Opossum) and performed gene expression profiling of aberrant dermal lymphatic vessels. Expression studies and functional analysis in zebrafish and mice revealed one candidate, ArfGAP with RhoGAP domain, Ankyrin repeat and PH domain 3 (ARAP3), which is down-regulated in HLT mouse lymphatic vessels and necessary for lymphatic vascular development in mice and zebrafish. We position this known regulator of cell behaviour during migration as a mediator of the cellular response to Vegfc signalling in lymphatic endothelial cells in vitro and in vivo. Our data refine common mechanisms that are likely to contribute during both development and the pathogenesis of lymphatic vascular disorders.

Genes / Markers
Figures
No images available
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu4602
    Point Mutation
    hu5333TgTransgenic Insertion
      kca4TgTransgenic Insertion
        nz101TgTransgenic Insertion
          s843TgTransgenic Insertion
            s896TgTransgenic Insertion
              uq1bhTgTransgenic Insertion
                y1TgTransgenic Insertion
                  y7TgTransgenic Insertion
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Target Reagent Reagent Type
                    arap3MO3-arap3MRPHLNO
                    arap3MO2-arap3MRPHLNO
                    flt4MO3-flt4MRPHLNO
                    ilkMO1-ilkMRPHLNO
                    ilkMO2-ilkMRPHLNO
                    kdrMO1-kdrMRPHLNO
                    kdrlMO4-kdrlMRPHLNO
                    limch1bMO1-limch1bMRPHLNO
                    limch1bMO2-limch1bMRPHLNO
                    mmp17aMO1-mmp17aMRPHLNO
                    1 - 10 of 22
                    Show
                    Fish
                    Antibodies
                    No data available
                    Orthology
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    DsRedEFGDsRed
                    EGFPEFGEGFP
                    GAL4EFGGAL4
                    mCherryEFGmCherry
                    RFPEFGRFP
                    1 - 5 of 5
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                    Mapping