Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice

Hiroaki Masuda, Hirotaka Chikuda, Tatsuo Suga, Hiroshi Kawaguchi, Makoto Kuro-o

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Mice carrying a loss-of-function mutation in the klotho gene (KL -/- mice) develop ageing-like symptoms around 4 weeks after birth and suffer from multiple age-related disorders observed in humans, including osteoporosis, arteriosclerosis, and pulmonary emphysema. The klotho gene encodes a single-pass transmembrane protein that may function in signaling pathways that suppress ageing. To investigate the ability of Klotho to regulate the development of ageing-related disorders, we established an inducible Klotho expression system using KL-/- mice carrying an exogenous klotho gene fused to the mouse metallothionein-I promoter, in which Klotho expression was dependent on zinc water feeding. We demonstrate that many advanced ageing-like KL-/- phenotypes were restored to normal whenever Klotho expression was induced. Conversely, decreasing Klotho expression in these rescued KL -/- mice induced several ageing-like KL-/- phenotypes. Our data indicate that Klotho may be effective in the treatment of multiple age-related disorders and is essential for maintaining animals free of these disorders.

Original languageEnglish (US)
Pages (from-to)1274-1283
Number of pages10
JournalMechanisms of Ageing and Development
Volume126
Issue number12
DOIs
StatePublished - Dec 1 2005

Keywords

  • Ageing
  • Klotho
  • Transgenic mice

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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