Skip to main content
Log in

Identification and expression analysis of the zebrafish orthologue of Klotho

  • Short Communication
  • Published:
Development Genes and Evolution Aims and scope Submit manuscript

Abstract

Klotho is an aging suppressor gene. In mice, loss of Klotho function causes accelerated aging while increased Klotho expression increases longevity. This study aimed to identify and characterize the orthologue of Klotho in zebrafish, a powerful model organism for the investigation of development and human disease. Zebrafish klotho was identified by a bioinformatics approach, and cloning and sequencing of klotho cDNA confirmed the in silico analysis. The zebrafish Klotho protein has a structure similar to human and mouse Klotho, but it lacks an apparent secretory signal sequence. We can find no evidence of an alternative transcript isoform lacking the transmembrane domain coding sequence as seen in mammals. RT-PCR revealed the expression of klotho during embryonic development and in a wider variety of adult tissues than in mouse. Quantitative real-time RT-PCR demonstrated the relative gene expression profile of zebrafish Klotho during embryogenesis and in adult tissues. In situ hybridization showed an apparently diffuse signal of klotho mRNA expression in the adult zebrafish testis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  • Bloch L, Sineshchekova O, Reichenbach D, Reiss K, Saftig P, Kuro-o M, Kaether C (2009) Klotho is a substrate for alpha-, beta- and gamma-secretase. FEBS Lett 583(19):3221–3224

    Article  PubMed  CAS  Google Scholar 

  • Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96(6):857–868

    Article  PubMed  CAS  Google Scholar 

  • Chateau MT, Araiz C, Descamps S, Galas S (2010) Klotho interferes with a novel FGF-signalling pathway and insulin/Igf-like signalling to improve longevity and stress resistance in Caenorhabditis elegans. Aging (Albany NY) 2(9):567–581

    CAS  Google Scholar 

  • Felsenstein J (2005) PHYLIP (Phylogeny Inference Package) version 3.6. Distributed by the author. Department of Genome Sciences, University of Washington, Seattle

  • Gouet P, Courcelle E, Stuart DI, Metoz F (1999) ESPript: multiple sequence alignments in PostScript. Bioinformatics 15:305–308

    Article  PubMed  CAS  Google Scholar 

  • Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, Goetz R, Mohammadi M, White KE, Econs MJ (2007) A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest 117(9):2684–2691

    Article  PubMed  CAS  Google Scholar 

  • Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N et al (2004) Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Lett 565(1–3):143–147

    Article  PubMed  CAS  Google Scholar 

  • Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM (2002) Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419(6904):316–321

    Article  PubMed  CAS  Google Scholar 

  • Kuro-o M (2008) Klotho as a regulator of oxidative stress and senescence. Biol Chem 389(3):233–241

    Article  PubMed  CAS  Google Scholar 

  • Kuro-o M (2009) Klotho and aging. Biochim Biophys Acta 1790(10):1049–1058

    PubMed  CAS  Google Scholar 

  • Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390(6655):45–51

    Article  PubMed  CAS  Google Scholar 

  • Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M (2005) Suppression of aging in mice by the hormone Klotho. Science 309(5742):1829–1833

    Article  PubMed  CAS  Google Scholar 

  • Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW, Kuro-o M (2006) Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem 281(10):6120–6123

    Article  PubMed  CAS  Google Scholar 

  • Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y (1998) Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun 242(3):626–630

    Article  PubMed  CAS  Google Scholar 

  • Newman M, Tucker B, Nornes S, Ward A, Lardelli M (2009) Altering presenilin gene activity in zebrafish embryos causes changes in expression of genes with potential involvement in Alzheimer's disease pathogenesis. J Alzheimers Dis 16(1):133–147

    PubMed  CAS  Google Scholar 

  • Okabe M, Graham A (2004) The origin of the parathyroid gland. Proc Natl Acad Sci USA 101(51):17716–17719

    Article  PubMed  CAS  Google Scholar 

  • Polanska UM, Edwards E, Fernig DG, Kinnunen TK (2011) Co-operation of FGF receptor and Klotho is involved in excretory canal development and regulation of metabolic homeostasis in C. elegans. J Biol Chem 286:5657–5666

    Article  PubMed  CAS  Google Scholar 

  • Shiraki-Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, Nagai R, Kuro-o M, Nabeshima Y (1998) Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Lett 424(1–2):6–10

    Article  PubMed  CAS  Google Scholar 

  • Tamme R, Mills K, Rainbird B, Nornes S, Lardelli M (2001) Simple, directional cDNA cloning for in situ transcript hybridization screens. Biotechniques 31(4):938–942, 44, 46

    PubMed  CAS  Google Scholar 

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 24:4876–4882

    Article  Google Scholar 

  • Westerfield M (2000) The zebrafish book, 4th edn: a guide for the laboratory use of zebrafish (Danio rerio). University of Oregon Press, Eugene

Download references

Acknowledgements

All of the animal experiments were carried out under the auspices of the Animal Ethics Committee of the University of Adelaide. Y.S. was supported by a scholarship from the Rotary Foundation and the research was funded by the Discipline of Genetics and the School of Molecular and Biomedical Sciences at the University of Adelaide.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuya Sugano.

Additional information

Communicated by M. Hammerschmidt

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugano, Y., Lardelli, M. Identification and expression analysis of the zebrafish orthologue of Klotho. Dev Genes Evol 221, 179–186 (2011). https://doi.org/10.1007/s00427-011-0367-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00427-011-0367-3

Keywords

Navigation