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*
  • Inflammation/genetics
  • Inflammation/metabolism
  • Glucuronidase/genetics
  • Glucuronidase/metabolism*
  • Animals, Genetically Modified
  • Mutation
  • Vascular Calcification/genetics
  • Vascular Calcification/metabolism*
  • Vascular Calcification/mortality
  • Heart
  • Kidney/metabolism
  • Animals
  • Fibroblast Growth Factors/genetics
  • Fibroblast Growth Factors/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Male
  • RNA-Seq
  • Longevity/genetics*
  • Gene Knockout Techniques
  • Signal Transduction/genetics
  • Myocardium/metabolism
(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)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
Fish
Antibodies
No data available
Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
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. (2019) αKlotho Regulates Age-Associated Vascular Calcification and Lifespan in Zebrafish. Cell Reports. 28:2767-2776.e5.