PUBLICATION

Vitamin K reduces hypermineralisation in zebrafish models of PXE and GACI

Authors
Mackay, E.W., Apschner, A., Schulte-Merker, S.
ID
ZDB-PUB-150312-4
Date
2015
Source
Development (Cambridge, England)   142: 1095-101 (Journal)
Registered Authors
Apschner, Alexander, Schulte-Merker, Stefan
Keywords
ABCC6, Mineralisation, PXE, Vitamin K, Zebrafish
MeSH Terms
  • Transgenes/genetics
  • Mutation/genetics
  • DNA Primers/genetics
  • Anthraquinones
  • Vitamin K/genetics*
  • Vitamin K/metabolism
  • In Situ Hybridization
  • Warfarin
  • Calcinosis/genetics*
  • Calcinosis/metabolism
  • Pseudoxanthoma Elasticum/genetics*
  • Pseudoxanthoma Elasticum/metabolism
  • Chromosomes, Artificial, Bacterial
  • Vascular Calcification/genetics*
  • Vascular Calcification/metabolism
  • Animals
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Zebrafish/genetics*
  • ATP-Binding Cassette Transporters/genetics*
  • ATP-Binding Cassette Transporters/metabolism
(all 21)
PubMed
25758222 Full text @ Development
CTD
25758222
Abstract
The mineralisation disorder pseudoxanthoma elasticum (PXE) is associated with mutations in the transporter protein ABCC6. Patients with PXE suffer from calcified lesions in the skin, eyes and vasculature, and PXE is related to a more severe vascular calcification syndrome called generalised arterial calcification of infancy (GACI). Mutations in ABCC6 are linked to reduced levels of circulating vitamin K. Here, we describe a mutation in the zebrafish (Danio rerio) orthologue abcc6a, which results in extensive hypermineralisation of the axial skeleton. Administration of vitamin K to embryos was sufficient to restore normal levels of mineralisation. Vitamin K also reduced ectopic mineralisation in a zebrafish model of GACI, and warfarin exacerbated the mineralisation phenotype in both mutant lines. These data suggest that vitamin K could be a beneficial treatment for human patients with PXE or GACI. Additionally, we found that abcc6a is strongly expressed at the site of mineralisation rather than the liver, as it is in mammals, which has significant implications for our understanding of the function of ABCC6.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu4581
    Point Mutation
    hu4958
      Point Mutation
      hu10967TgTransgenic Insertion
        nkuasgfp1aTgTransgenic Insertion
          nkuasrfp1aTgTransgenic Insertion
            zf132TgTransgenic Insertion
              1 - 6 of 6
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              Human Disease / Model
              Sequence Targeting Reagents
              No data available
              Fish
              Antibodies
              No data available
              Orthology
              Gene Orthology
              abcc6a
              1 - 1 of 1
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              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              GAL4FFEFGGAL4FF
              GFPEFGGFP
              RFPEFGRFP
              1 - 4 of 4
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              Mapping
              No data available