Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice

Shun Ai Li, Masami Watanabe, Hiroshi Yamada, Atsushi Nagai, Masahiro Kinuta, Kohji Takei

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

Klotho mutant mouse (kl-/-), a mouse model for human aging, exhibits various phenotypes in a wide range of organs including arteriosclerosis, neural degeneration, skin and gonadal atrophy, pulmonary emphysema, calcification of soft tissues, and cognition impairment. Klotho mRNA, however, is expressed only in brain, kidney, reproductive organs, pituitary gland, and parathyroid gland. Therefore it remains to be elucidated how lack of Klotho protein in these limited organs leads to the variety of phenotypes. To shed light on mechanisms by which Klotho protein acts on distant targets, we examined localization of Klotho protein in brain, kidney, and reproductive organs, and analyzed brain and kidney in kl-/- mice searching for changes in target regions in these organs. In brain, Klotho proteins were localized at choroid plexus, where the proteins were dominantly localized at the apical plasma membrane of ependymal cells. In kl-/- brain, reduction of synapses was evident in hippocampus, suggesting a role of Klotho as a humoral factor in cerebrospinal fluid. Klotho proteins in kidney localized at distal renal tubules. Interestingly, in kl-/- mice, type IIa Na/phosphate (Pi) cotransporters, which function at the proximal renal tubules in reabsorption of phosphate ions, were translocated. This suggests that Klotho protein in kidney is implicated in calcium homeostasis which regulates localization of type IIa Na/Pi cotransporters via parathyroid hormone (PTH). Klotho proteins in reproductive organs were expressed only in mature germ cells, although in kl-/- mice germ cell maturation was arrested at earlier stages. Thus, Klotho proteins not only function as a humoral factor, but also are implicated in hormonal regulation, which may explain why mutation of klotho gene results in a variety of phenotypes.

Original languageEnglish
Pages (from-to)91-99
Number of pages9
JournalCell Structure and Function
Volume29
Issue number4
DOIs
Publication statusPublished - Dec 2004

Fingerprint

Kidney
Brain
Phenotype
Germ Cells
Distal Kidney Tubule
Phosphates
Pulmonary Emphysema
Proximal Kidney Tubule
Choroid Plexus
Parathyroid Glands
klotho protein
Arteriosclerosis
Pituitary Gland
Parathyroid Hormone
Synapses
Cognition
Atrophy
Cerebrospinal Fluid
Hippocampus
Homeostasis

Keywords

  • Aging
  • Choroid plexus
  • Germ cell
  • Klotho
  • Renal tubule

ASJC Scopus subject areas

  • Physiology
  • Structural Biology
  • Cell Biology

Cite this

Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. / Li, Shun Ai; Watanabe, Masami; Yamada, Hiroshi; Nagai, Atsushi; Kinuta, Masahiro; Takei, Kohji.

In: Cell Structure and Function, Vol. 29, No. 4, 12.2004, p. 91-99.

Research output: Contribution to journalArticle

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