Identification and expression analysis of the zebrafish orthologue of Klotho

Sugano, Yuya; Lardelli, Michael

doi:10.1007/s00427-011-0367-3

Cited by 15 publications

(12 citation statements)

References 19 publications

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“…In a recently published study that used RT-PCR and qRT-PCR methods, αklotho expression could be detected in zebrafish embryos as early as 5 hpf [22]. We show here that zebrafish αklotho could be detected in 24 hpf embryos by whole-mount in situ hybridization (Figure 5A).…”

Section: αKlotho Expressionsupporting

confidence: 65%

Expression of fgf23 and klotho in developing embryonic tissues and adult kidney of the zebrafish, Danio rerio

Mangos

Amaral

Faul

et al. 2012

Nephrology Dialysis Transplantation

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Fibroblast growth factor 23 (FGF23) is an endocrine hormone that is secreted by bone and acts on the kidney and parathyroid glands to regulate phosphate homeostasis. The effects of FGF23 on phosphate homeostasis are mediated by binding to FGF receptors and their coreceptor, αklotho, which are abundantly expressed in the kidney and parathyroid glands. However, the mechanisms of how FGF23 regulates phosphate handling in the proximal tubule are unclear because αklotho is primarily expressed in the distal nephron in humans and rodents. The purpose of this study was to gain additional insight into the FGF23-αklotho system by investigating the spatial and temporal aspects of the expression of fgf23 and αklotho in the zebrafish, Danio rerio. Here, we report that zebrafish fgf23 begins to be expressed after organogenesis and is continually expressed into adulthood in the corpuscles of Stannius, which are endocrine glands that lie in close proximity to the nephron and are thought to contribute to calcium and phosphate homeostasis in fish. Zebrafish αklotho expression can be detected by 24-h postfertilization in the brain, pancreas and the distal pronephros, and by 56-h postfertilization in liver. Expression in the distal pronephros persists throughout development, and by Day 5, there is also strong expression in the proximal pronephros. αklotho continues to be expressed in the tubules of the metanephros of the adult kidney. These data indicate conservation of the FGF23-αklotho system across species and suggest a likely role for αklotho in the proximal and distal tubules.

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Section: αKlotho Expressionsupporting

confidence: 65%

Expression of fgf23 and klotho in developing embryonic tissues and adult kidney of the zebrafish, Danio rerio

Mangos

Amaral

Faul

et al. 2012

Nephrology Dialysis Transplantation

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“…2). These results agree with previous findings in zebrafish showing that αklotho transcripts were evident during early embryonic stages and gradually increased as development proceeded (Sugano and Lardelli 2011). Also in mouse, α Klotho immunoreactivity was initially observed at embryonic day 16 followed by an apparent induction after birth (Song et al 2014).…”

Section: Resultssupporting

confidence: 93%

“…1 a). In mammals, N-terminal signal sequences have been described for both Klotho paralogs (Kuro-o et al 1997 ; Ito et al 2000 ) which is apparently lacking in zebrafish α Klotho (Sugano and Lardelli 2011 ) and also in the two Klotho paralogs in the nematode Caenorhabditis elegans (Château et al 2010 ). Using the protein prediction resource InterProScan (Finn et al 2017 ), we found a strong putative signal sequence for both killifish orthologs α Klotho (AA 1–18) and βKlotho (AA 1–25).…”

Section: Resultsmentioning

confidence: 99%

Phylogenetic analysis and expression profiling of the Klotho gene family in the short-lived African killifish Nothobranchius furzeri

et al. 2018

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Members of the Klotho gene family have been identified as modulators of the aging process. Deletion of αklotho in the mouse results in a syndrome resembling rapid human aging. Conversely, overexpression of αklotho extends mammalian lifespan. Here, we identify klotho orthologs in the vertebrate aging model Nothobranchius furzeri and provide a detailed spatio-temporal expression profile of both paralogs, α and βklotho, from embryogenesis until old age spanning the entire life cycle of the organism. Specifically, we observe low levels of expression of both paralogs during embryogenesis followed by a significant transcriptional induction as development proceeds. In adult killifish, αklotho is predominantly expressed in the liver, the kidney, and the developing pharyngeal teeth. Particularly high levels of αKlotho protein were identified in the kidney tubules, closely resembling mammalian expression patterns. Prominent βklotho expression was detected in the killifish intestine and liver. Overall, qRT-PCR analysis of Klotho members as a function of age revealed steady transcript levels, except for βklotho expression in the liver which was significantly downregulated with age. This spatio-temporal expression profiling may serve as a useful starting point to further investigate the distinct physiological roles of Klotho members during the aging process.Electronic supplementary materialThe online version of this article (10.1007/s00427-018-0619-6) contains supplementary material, which is available to authorized users.

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“…More details on the mouse Klotho gene and the identification of the human (96% homology) as well as the rat Klotho gene were reported 1 year later ; two distinct transcripts encoding membrane and secreted Klotho protein were characterized. Klotho has been identified not only in the zebrafish, Danio rerio, but two Klotho-like genes, klo1 and klo2, have also been identified in the nematode Caenorhabditis elegans (Polanska et al 2011, Sugano & Lardelli 2011, Mangos et al 2012. The corresponding KLO1 and KLO2 proteins lack a transmembrane domain.…”

Section: Klotho a Transmembrane Co-receptor And A Multifunctional Humentioning

confidence: 99%

Growth hormone and Klotho

Schmid

Neidert

Tschopp

et al. 2013

Journal of Endocrinology

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Acromegaly is characterized by excessively high GH and IGF1 levels. Recent data suggest that soluble Klotho (sKlotho) is also elevated in patients with active acromegaly. sKlotho decreases towards normal following removal of the GH-producing pituitary adenoma. The Klotho gene was identified in mice following its accidental disruption by ectopic DNA. It is an ageing suppressor gene of restricted expression (mainly in kidneys, brain, and parathyroid and pituitary glands) encoding a transmembrane protein, mKlotho. mKlotho serves as a co-receptor in fibroblast growth factor 23 (FGF23) signalling. FGF23 promotes urinary phosphate excretion and inhibits the synthesis of calcitriol. The ectodomain of mKlotho is enzymatically released to result in a humoral factor, sKlotho, which exerts systemic effects (on ion channels and signalling pathways), possibly by working as an enzyme that modifies glycans of cell surface glycoproteins. GH enhances renal phosphate reabsorption and calcitriol production, i.e. exerts effects in the proximal tubule opposing those attributed to mKlotho, and attenuates calciuria in the distal tubule similar to sKlotho. sKlotho can be measured in extracellular fluids (serum, urine and cerebrospinal fluid (CSF)) by an ELISA. In line with predominant expression of Klotho in kidneys and choroid plexus, concentrations of sKlotho are particularly high in urine and CSF. Determination of sKlotho in serum and urine (both presumably reflecting GH action on the kidneys) could be used as a supplementary tool in the diagnosis and follow-up of patients with acromegaly. The question arises whether GH exerts selected actions via modifying activities of Klotho.

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Identification and expression analysis of the zebrafish orthologue of Klotho

Cited by 15 publications

References 19 publications

Expression of fgf23 and klotho in developing embryonic tissues and adult kidney of the zebrafish, Danio rerio

Expression of fgf23 and klotho in developing embryonic tissues and adult kidney of the zebrafish, Danio rerio

Phylogenetic analysis and expression profiling of the Klotho gene family in the short-lived African killifish Nothobranchius furzeri

Growth hormone and Klotho

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