PUBLICATION

αKlotho Regulates Age-Associated Vascular Calcification and Lifespan in Zebrafish

Authors
Singh, A.P., Sosa, M.X., Fang, J., Shanmukhappa, S.K., Hubaud, A., Fawcett, C.H., Molind, G.J., Tsai, T., Capodieci, P., Wetzel, K., Sanchez, E., Wang, G., Coble, M., Tang, W., Cadena, S.M., Fishman, M.C., Glass, D.J.
ID
ZDB-PUB-190912-13
Date
2019
Source
Cell Reports   28: 2767-2776.e5 (Journal)
Registered Authors
Fawcett, Caroline, Fishman, Mark C., Hubaud, Alexis, Tang, Wenlong, Wang, Guangliang (Johnny)
Keywords
FGF23, Klotho, aging, calcification, cardiovascular system, zebrafish, αKlotho
MeSH Terms
  • Osteogenesis/genetics*
  • Myocardium/metabolism
  • Vascular Calcification/genetics
  • Vascular Calcification/metabolism*
  • Vascular Calcification/mortality
  • Male
  • Animals
  • Longevity/genetics*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Kidney/metabolism
  • Signal Transduction/genetics
  • Heart
  • Fibroblast Growth Factors/genetics
  • Fibroblast Growth Factors/metabolism
  • Glucuronidase/genetics
  • Glucuronidase/metabolism*
  • Mutation
  • Gene Knockout Techniques
  • Inflammation/genetics
  • Inflammation/metabolism
  • Animals, Genetically Modified
  • RNA-Seq
(all 23)
PubMed
31509740 Full text @ Cell Rep.
Abstract
The hormone αKlotho regulates lifespan in mice, as knockouts die early of what appears to be accelerated aging due to hyperphosphatemia and soft tissue calcification. In contrast, the overexpression of αKlotho increases lifespan. Given the severe mouse phenotype, we generated zebrafish mutants for αklotho as well as its binding partner fibroblast growth factor-23 (fgf23). Both mutations cause shortened lifespan in zebrafish, with abrupt onset of behavioral and degenerative physical changes at around 5 months of age. There is a calcification of vessels throughout the body, most dramatically in the outflow tract of the heart, the bulbus arteriosus (BA). This calcification is associated with an ectopic activation of osteoclast differentiation pathways. These findings suggest that the gradual loss of αKlotho found in normal aging might give rise to ectopic calcification.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf3212
    Small Deletion
    zf3213
      Small Deletion
      zf3214
        Insertion
        zf3215
          Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          fgf23CRISPR1-fgf23CRISPR
          klCRISPR1-klCRISPR
          1 - 2 of 2
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          Fish
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          No data available
          Mapping
          No data available