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Mutation of the mouse klotho gene leads to a syndrome resembling ageing

Nature volume 390, pages 45–51 (1997)Cite this article

Abstract

A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes. A defect in klotho gene expression in the mouse results in a syndrome that resembles human ageing, including a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema. The gene encodes a membrane protein that shares sequence similarity with the β-glucosidase enzymes. The klotho gene product may function as part of a signalling pathway that regulates ageing in vivo and morbidity in age-related diseases.

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Figure 1: Macroscopic findings of klotho mice (8 weeks old).
Figure 2: Short lifespan, growth retardation, and hypokinesis in kl/kl mice.
Figure 3: Histological analysis of kl/kl mice.
Figure 7: Rescue of the klotho mice by exogenous kl gene expression.
Figure 4: Identification of mouse klotho locus.
Figure 5: Expression of the mouse klotho gene.
Figure 6: Amino-acid sequences and primary structure of mouse KL protein and its human homologue.

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Acknowledgements

We thank E. Ozawa, T. Ishikawa, K. Hanaoka and I. Nonaka for earlier contributions to this work, T. Matsuzaki, S. Kameya and Y. Hiroi for maintaining mice, and H. Yamato and Y. Nagai for bone analyses.

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Authors and Affiliations

  1. Division of Molecular Genetics, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, 187, Tokyo, Japan

    Makoto Kuro-o, Yutaka Matsumura, Hiroki Aizawa, Takako Shiraki-Iida & Yo-ichi Nabeshima

  2. The 2nd Department of Internal Medicine, University of Gunma School of Medicine, 3-39-22, Showa, Maebashi, 371, Gunma, Japan

    Yutaka Matsumura, Hiroki Aizawa, Tatsuo Suga, Toshihiro Utsugi, Yoshio Ohyama, Masahiko Kurabayashi & Ryozo Nagai

  3. Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113, Tokyo, Japan

    Hiroshi Kawaguchi

  4. Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumakoto, 862, Japan

    Tadashi Kaname

  5. Lead Optimization Research Laboratory, Tanabe Seiyaku Co. Ltd, 2-2-50 Kawagishi, Toda, 335, Saitama, Japan

    Eisuke Kume & Hitoshi Iwasaki

  6. Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, 3-6-6 Asahimachi, Machidashi, 194, Tokyo, Japan

    Akihiro Iida & Takako Shiraki-Iida

  7. Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, 118 Shimotagari, Nagaizumi, Sunto, 411, Shizuoka, Japan

    Satoshi Nishikawa

  8. Core Research for Evolutional Science & Technology (CREST), JRDC and,

    Ryozo Nagai & Yo-ichi Nabeshima

  9. Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, 565, Osaka, Japan

    Yo-ichi Nabeshima

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  1. Makoto Kuro-o
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  6. Toshihiro Utsugi
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  15. Ryozo Nagai
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  16. Yo-ichi Nabeshima
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Corresponding authors

Correspondence to Makoto Kuro-o or Yo-ichi Nabeshima.

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Kuro-o, M., Matsumura, Y., Aizawa, H. et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390, 45–51 (1997). https://doi.org/10.1038/36285

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